Search

The highly polygenic and pleiotropic nature of behavioural traits, psychiatric disorders and structural and functional brain phenotypes complicate mechanistic interpretation of related genome‐wide association study (GWAS) signals, thereby obscuring underlying causal biological processes. We propose genomic principal and independent component analysis (PCA, ICA) to decompose a large set of univariate GWAS statistics of multimodal brain traits into more interpretable latent genomic components. Here we introduce and evaluate this novel methods various analytic parameters and reproducibility across independent samples. Two UK Biobank GWAS summary statistic releases of 2240 imaging‐derived phenotypes (IDPs) were retrieved. Genome‐wide beta‐values and their corresponding standard‐error scaled z‐values were decomposed using genomic PCA/ICA. We evaluated variance explained at multiple dimensions up to 200. We tested the inter‐sample reproducibility of output of dimensions 5, 10, 25 and 50. Reproducibility statistics of the respective univariate GWAS served as benchmarks. Reproducibility of 10‐dimensional PCs and ICs showed the best trade‐off between model complexity and robustness and variance explained (PCs: |rz − max| = 0.33, |rraw − max| = 0.30; ICs: |rz − max| = 0.23, |rraw − max| = 0.19). Genomic PC and IC reproducibility improved substantially relative to mean univariate GWAS reproducibility up to dimension 10. Genomic components clustered along neuroimaging modalities. Our results indicate that genomic PCA and ICA decompose genetic effects on IDPs from GWAS statistics with high reproducibility by taking advantage of the inherent pleiotropic patterns. These findings encourage further applications of genomic PCA and ICA as fully data‐driven methods to effectively reduce the dimensionality, enhance the signal to noise ratio and improve interpretability of high‐dimensional multitrait genome‐wide analyses. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Areca nut (AN) is an addictive substance widely used in different world regions. There are several side effects associated with the use of AN, which have already been reported. However, the reports on hepatotoxicity of AN are sporadic and non‐conclusive. In the present case report, we investigated the hepatotoxicity of AN in a four‐year‐old Iranian girl who was transferred to our medical center with abdominal pain, vomiting, diarrhea, fever, and other symptoms such as hematuria, decreased mental status, multiple seizure episodes. After a comprehensive evaluation, it was concluded that these signs and symptoms were all attributed to AN consumption, which was given by her mother to control diarrhea. Eventually, the patient medical conditions were managed successfully, and she survived by intense medical care. In conclusion, we suggest AN should be considered a potential hepatotoxic agent. [ABSTRACT FROM AUTHOR]

A two‐degrees‐of‐freedom (2DOF) dual‐rotor axial‐flux induction motor (2DOF‐DRAFIM) is proposed with independent movement capability of rotors and its performance is evaluated in detail. First, using the analytical equations, the steady‐state model of the motor is presented and the electrical equivalent circuit is extracted along with an electromagnetic design algorithm for the proposed motor. In the next step, using two‐dimensional and three‐dimensional finite element modelling (FEM), the performance of the proposed motor is investigated. The results of the experimental measurements on the manufactured prototype confirm the validity of the results of theoretical modelling and finite element simulations. The proposed structure provides some unique features. One of the fascinating behaviours of the proposed 2DOF‐DRAFIM is that the higher‐speed rotor produces higher output torque and the lower‐speed rotor has lower torque. In this regard, the 2DOF structure can be considered a potential concept for electric vehicles (EVs) without needing a conventional mechanical differential. [ABSTRACT FROM AUTHOR]

Key Clinical Message: A patient presented with edema, ascites and jaundice. Histologic report was consistent with Celiac Disease. Liver biopsy commensurate with Glycogen storage disease III, which was confirmed by genetic testing. A gluten‐free diet was initiated. After 2 months, ascites was relieved, hepatic function was improved, and hepatic size reduced. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Most children with nephrotic syndrome heal without any sequelae. However, rare life‐threatening complications such as thromboembolism may occur in pediatric nephrotic syndrome and should be considered in those with a new‐onset neurologic deficit. The thromboembolism (TE) as a complication of nephrotic syndrome (NS) is rare and serious, and may involve renal, cerebral, pulmonary, or peripheral venous and/or arterial thrombosis. Here, we describe a 4.5‐year‐old male with a history of nephrotic syndrome, who developed hemorrhagic stroke in the territory of middle cerebral artery (MCA). [ABSTRACT FROM AUTHOR]

Key Clinical Message: ERCP is a safe and effective method for managing biliary obstruction in children. A case report illustrates successful removal of a bile duct stone in a 5‐year‐old child using ERCP. Pediatric ERCP is a viable option for treating biliary diseases in well‐equipped centers, alongside other approaches. We describe a 5‐year‐old child with extrahepatic biliary stone who successfully underwent endoscopic retrograde cholangiopancreatography for stone removal. He suffered from persistent colicky abdominal pain accompanied by fever that confirmed biliary stone. ERCP along with other methods, can be considered a safe procedure for managing BD in children. [ABSTRACT FROM AUTHOR]

This study aimed to produce and characterize eco‐friendly SSPS nanocomposites incorporated with various concentrations of TiO2 nanoparticles (NPs) (1%, 3%, and 7%). The antimicrobial activity of the nanocomposite films against five strains of pathogenic bacteria was examined. Salmonella typhi PTCC 1609 was the most sensitive species to TiO2 NPs at concentrations equal to the synthetic antibiotic. The migration of TiO2 to ethanol and acetic acid, as two food simulants increased when the initial nano‐TiO2 content increased. The release profiles for TiO2 in two simulants of ethanol and acetic acid indicated a non‐Fickian release, and the release kinetics were concentration‐dependent. SSPS/TiO2 nanocomposites degraded easily and thus have the potential to be applied as an eco‐friendly packaging system. Oral administration of doses of 1, 12.5, 25, 50, and 75 mg/kg TiO2 revealed that the dose of 50 and 75 mg/kg increased malondialdehyde (p <.001) concentration in the liver tissue. In addition, it decreased glutathione (p <.001) concentration in the liver tissue. [ABSTRACT FROM AUTHOR]

Bacterial membrane barrier provides a cytoplasmic environment for organelles of bacteria. The membrane is composed of lipid compounds containing phosphatide protein and a minimal amount of sugars, and is responsible for intercellular transfers of chemicals. Several antimicrobials have been found that affect bacterial cytoplasmic membranes. These compounds generally disrupt the organization of the membrane or perforate it. By destroying the membrane, the drugs can permeate and replace the effective macromolecules necessary for cell life. Furthermore, they can disrupt electrical gradients of the cells through impairment of the membrane integrity. In recent years, considering the spread of microbial resistance and the side effects of antibiotics, natural antimicrobial compounds have been studied by researchers extensively. These molecules are the best alternative for controlling bacterial infections and reducing drug resistance due to the lack of severe side effects, low cost of production, and biocompatibility. Better understanding of the natural compounds' mechanisms against bacteria provides improved strategies for antimicrobial therapies. In this review, natural products with antibacterial activities focusing on membrane damaging mechanisms were described. However, further high‐quality research studies are needed to confirm the clinical efficacy of these natural products. [ABSTRACT FROM AUTHOR]

Angiogenesis, inflammation and endothelial cells' migration and proliferation exert fundamental roles in different diseases. However, more studies are needed to identify key proteins and pathways involved in these processes. Aflibercept has received the approval of the US Food and Drug Administration (FDA) for the treatment of wet AMD and colorectal cancer. Moreover, the effect of Aflibercept on VEGFR2 downstream signalling pathways has not been investigated yet. Here, we integrated text mining data, protein‐protein interaction networks and multi‐experiment microarray data to specify candidate genes that are involved in VEGFA/VEGFR2 signalling pathways. Network analysis of candidate genes determined the importance of the nominated genes via different centrality parameters. Thereupon, several genes—with the highest centrality indexes—were recruited to investigate the impact of Aflibercept on their expression pattern in HUVEC cells. Real‐time PCR was performed, and relative expression of the specific genes revealed that Aflibercept modulated angiogenic process by VEGF/PI3KA/AKT/mTOR axis, invasion by MMP14/MMP9 axis and inflammation‐related angiogenesis by IL‐6‐STAT3 axis. Data showed Aflibercept simultaneously affected these processes and determined the nominated axes that had been affected by the drug. Furthermore, integrating the results of Aflibercept on expression of candidate genes with the current network analysis suggested that resistance against the Aflibercept effect is a plausible process in HUVEC cells. [ABSTRACT FROM AUTHOR]

Aging, the greatest risk factor for Alzheimer's disease (AD), may lead to the accumulation of somatic mutations in neurons. We investigated whether somatic mutations, specifically in longer genes, are implicated in AD etiology. First, we modeled the theoretical likelihood of genes being affected by aging‐induced somatic mutations, dependent on their length. We then tested this model and found that long genes are indeed more affected by somatic mutations and that their expression is more frequently reduced in AD brains. Furthermore, using gene‐set enrichment analysis, we investigated the potential consequences of such long gene disruption. We found that long genes are involved in synaptic adhesion and other synaptic pathways that are predicted to be inhibited in the brains of AD patients. Taken together, our findings indicate that long gene–dependent synaptic impairment may contribute to AD pathogenesis. [ABSTRACT FROM AUTHOR]

Parechoviruses are emerging pathogens of humans often affecting the pediatric age group, with a growing line of evidence implicating them as agents of a broad spectrum of clinical syndromes in adults. However, because many clinicians are not familiar with the manifestation of the infections, they are not included in the list of diagnostic pathogens. Furthermore, due to the indistinguishable feature of the infection compared with other common pathogens, a large number of cases are likely to go unchecked. Some may develop asymptomatic infection and recover without overt clinical disease. In this manuscript, we reviewed available literature on parechovirus infection in adult and summarized information relating to epidemiology, clinical manifestation, laboratory diagnosis, and therapeutics. The information provided should help in early case detection and support an evidence‐based clinical decision. Highlights: Human parechoviruses have been the etiologic agents of many clinical syndromes in children, and are increasingly recognized as agents of various illnesses in adults. However, since they are not included in the list of priority pathogens in most clinical settings, they are only rarely considered when the list of other common pathogens is exhausted. This, coupled with nonspecific clinical presentation makes it difficult to make the diagnosis, and many cases go undiagnosed, while some develop complications. In this article, we reviewed the literature on parechovirus infection in adults to help early case detection in the clinical setting and guides epidemiological studies. [ABSTRACT FROM AUTHOR]

The application of (bio)wastes as alternatives to expensive existing catalysts is an approach that can be used to reduce environmental pollution problems. Animal bone wastes have attracted much attention as environmentally friendly heterogeneous catalysts for chemical transformations such as transesterification, oxidation, and biofuel production, owing to the substantial availability of valuable hydroxyapatite (HAp) in their structure. Most catalysts based on bone can be prepared easily by calcination. High‐temperature calcination yields highly active catalysts. Heterogeneous catalysts prepared from these renewable sources could also simply be reused and recovered without any important loss of catalytic performance. This paper reviews past efforts and recent progress on the development of different eco‐friendly catalysts derived from bone waste and some of their catalyzed chemical transformations. However, future challenges focus on crediting the conversion of unusable wastes to valuable sources to meet global requirements © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

One of the most abundant wastes from all around the world is nutrient resources. Among them, fruits, their extracts, and residues comprise a major portion, which contain many valuable components that get lost during disposal or become burden on the shrinking landfills. These concerns are addressed by seeking sustainable processing methods that would have a minimal environmental impact. The crops contain renewable chemicals which are useful for catalysis, wastewater treatment, or preparation of nanomaterials; there has been an upsurge for the industrial applications of (nano)materials as their environmental and catalytic appliances is a fascinating subject to design cheaper and safer catalytic systems. Due to the excellent chemical properties of the fruit extracts, they have garnered attention as cost‐effective catalysts and support materials. This review focuses on the preparation of (nano)materials and their catalytic and environmental applications and highlights the potential appliances and industrial benefits derived from these low‐cost renewable and sustainable greener sources thus essentially converting waste into wealth. [ABSTRACT FROM AUTHOR]

Molecular mechanisms underlying Alzheimer's disease (AD) are difficult to investigate, partly because diagnosis lags behind the insidious pathological processes. Therefore, identifying AD neuroimaging markers and their genetic modifiers may help study early mechanisms of neurodegeneration. We aimed to identify brain regions of the highest vulnerability to AD using a data‐driven search in the AD Neuroimaging Initiative (ADNI, n = 1,100 subjects), and further explored genetic variants affecting this critical brain trait using both ADNI and the younger UK Biobank cohort (n = 8,428 subjects). Tensor‐Based Morphometry (TBM) and Independent Component Analysis (ICA) identified the limbic system and its interconnecting white‐matter as the most AD‐vulnerable brain feature. Whole‐genome analysis revealed a common variant in SHARPIN that was associated with this imaging feature (rs34173062, p = 2.1 × 10−10). This genetic association was validated in the UK Biobank, where it was correlated with entorhinal cortical thickness bilaterally (p =.002 left and p = 8.6 × 10−4 right), and with parental history of AD (p = 2.3 × 10−6). Our findings suggest that neuroanatomical variation in the limbic system and AD risk are associated with a novel variant in SHARPIN. The role of this postsynaptic density gene product in β1‐integrin adhesion is in line with the amyloid precursor protein (APP) intracellular signaling pathway and the recent genome‐wide evidence. [ABSTRACT FROM AUTHOR]

Objective: Lavender is an aromatic shrub belonging to the Lamiaceae family. The flowers and leaves in different forms of extracts are used as herbal medicine. The accumulation of amyloid beta (Aβ) plaques, reduction of acetylcholine due to hyperactivity of acetylcholinesterase, and glutamate neurotoxicity are known to be involved in decreased level of cognitive function. In our previous study, we proved that the aqueous extract of lavender improves learning and memory. This in vitro study was designed to evaluate antiaggregative, antioxidant, and antiacetylcholinesterase activities of the herbal medicine. Methods: Thin layer chromatography, high‐performance liquid chromatography, thioflavin, atomic force microscope (AFM), Elleman,and 2,2‐diphenyl‐1‐picryl hydrazyl techniques were used for qualitative analysis, quantitative analysis, antiaggregative characteristics, anti‐acetylcholinestrase activity and antioxidant activity of the lavender extract, respectively. Results: We found chromatographic peaks of caffeic acid and luteolin‐7‐glycosid in the lavender extract. Our results indicated that aqueous extract of lavender dose‐dependently inhibits the formation of Aβ aggregate. The AFM technique showed that lavender largely diminished the Aβ fibril formation. We also observed a considerable radical scavenging activity of the extract. Conclusions: Prevention of Aβ plaque formation and antioxidant activity along with nontoxic features of the lavender extract promise possible effectiveness of this plant on improving some neurological disorders including Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Influence and capital are two concepts used to evaluate scholarly outputs, and these can be measured using the Scholarly Capital Model as a modelling tool. The tool looks at the concepts of connectedness, venue representation, and ideational influence using centrality measures within a social network. This research used co‐authorships and h‐indices to investigate authors who have published papers in the field of information behaviour between 1980 and 2015 as extracted from Web of Science. The findings show a relationship between the authors’ connectedness and the venue (journal) representation. It could be seen that the venue (journal) influences the chance of citation, and equally, the prestige (centrality) of authors probably raises the citations of the journals. The research also shows a significant positive relationship between the venue representation and ideational influence. This means that a research work that is published in a highly cited journal will find more visibility and will receive more citations. [ABSTRACT FROM AUTHOR]

Cell replacement is a promising therapy for degenerative diseases like age-related macular degeneration (AMD). Since the human retina lacks regeneration capacity, much attention has been directed toward persuading for cells that can differentiate into retinal neurons. In this report, we have investigated reprogramming of the humanRPEcells and concerned the effect of donor age on the cellular fate as a critical determinant in reprogramming competence. We evaluated the effect of SOX2 over-expression in human neonatal and adult RPE cells in cultures. The coding region of human SOX2 gene was cloned into adeno-associated virus (AAV2) and primary culture of human neonatal/adult RPE cellswere infected by recombinant virus. De-differentiation of RPE to neural/retinal progenitor cells was investigated by quantitative real-time PCR and ICC for neural/retinal progenitor cells' markers. Gene expression analysis showed 80-fold and 12-fold over-expression for SOX2 gene in infected neonatal and adult hRPE cells, respectively. The fold of increase for Nestin in neonatal and adult hRPE cells was 3.8-fold and 2.5-fold, respectively. PAX6 expression was increased threefold and 2.5-fold in neonatal/adult treated cultures. Howbeit, we could not detect rhodopsin, and CHX10 expression in neonatal hRPE cultures and expression of rhodopsin in adult hRPE cells. Results showed SOX2 induced human neonatal/adult RPE cells to dedifferentiate toward retinal progenitor cells. However, the increased number of PAX6, CHX10, Thy1, and rhodopsin positive cells in adult hRPE treated cultures clearly indicated the considerable generation of neuro-retinal terminally differentiated cells. [ABSTRACT FROM AUTHOR]

The retinal pigment epithelium is a monolayer of highly specialized pigmented cells located between the neural retina and the Bruch's membrane of the choroid. RPE cells play a crucial role in the maintenance and function of the underlying photoreceptors. This study introduces a spontaneously arising human retinal pigment epithelial cell line, HRPE-2S, which was isolated from primary RPE cell culture of 2 days old male donor. We characterized morphology and functional properties of the new cell line. The immortalized cell line was maintained in culture for more than 70 passages and 240 divisions. The average doubling time of the cells was approximately 22 h and got freezed at 26th passage. The cell line expressed RPE-specific markers RPE65 and cell junction protein ZO1 as an epithelial cell marker. It also expressed CHX10, PAX6, Nestin, SOX2 as stem and retinal progenitor cell markers. Ki67 as a marker of cell proliferation was expressed in all HRPE-2S cells. It represented typical epithelial cobblestone morphology and did not phenotypically change through several passages. Stem cell-like aggregations (neurospheres) were observed in SEM microscopy. The cells represented high mitotic index. They could be viable under hypoxic conditions and serum deprivation. According to functional studies, the cell line exhibited stem cell-like behaviors with particular emphasis on its self-renewal capacity. LDH isoenzymes expression pattern confirmed the same cellular source for both of the HRPE-2S cells and primary RPE cells. Characteristics of HRPE-2S cells promise it as an in vitro model for RPE stem cell-based researches. J. Cell. Physiol. 232: 2626-2640, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Power system faults with the possibility of threatening public safety are of highest importance. High‐impedance faults (HIFs), considering the companionship with electrical arcs, occur on power distribution system feeders with close proximity to the population. The randomness, low current, non‐linearity and dependency towards network topology have commonly resulted in failed detection. Moreover, typical system events such as switching events have shown the same pattern which has led to false detection and major distrust in available detection schemes. In this study, a new HIF detection algorithm based on the concept of evidential reasoning (ER) has been proposed. The employment of various basic attributes with different advantages results in a wider detection scope and higher detection rates. The designed scheme has the ability to successfully detect and distinguish switching events from HIFs. Rigorous simulations via the IEEE 13‐Node standard distribution system and experimental real‐world HIF data acquired from southwest Tehran Distribution Company have provided proof to these claims. Simulation trials in low‐current single‐phase extensions have also shown promising results. Unaffectedness in regards to network topology, fault resistance values, fault position and lack of sufficient information regarding basic attributes are additional virtues of the proposed method. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a microvas-cular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgendy needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growdi factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More dian 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by signif-icandy higher rate of fluorophore spreading widi VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 µm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (M=7) showed significandy more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one tiiat might help to prevent retinal vascular leakage and proliferation in diabetic patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Synthetic polymers represent a modifiable class of materials that can serve as adjuvants to address challenges in numerous biomedical and medicinal chemistry applications including the delivery of siRNA. Polymer-based therapeutics offer unique challenges in both synthesis and characterization as compared to small molecule therapeutics. The ability to control the structure of the polymer is critical in creating a therapeutic. Reported herein, are batch and flow polymerization processes to produce amphiphilic terpolymers through a Lewis acid BF3OEt2-catalyzed polymerization. These processes focus on controlling reaction variables, which affect polymer structure in this rapid, exothermic, nonliving cationic polymerization. In addition to analytical characterization of the polymers, the in vivo activity of the polymer-siRNA conjugates is also highlighted-demonstrating that the method of synthesis does affect the in vivo activity of the resulting polymer conjugate. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1119-1129 [ABSTRACT FROM AUTHOR]

Vegetable oils have been deacidified using supercritical carbon dioxide and membrane processing. However, the pressures required are substantially greater than those used in industry. Therefore, the feasibility of using subcritical carbon dioxide (at much lower pressures) and membrane processing to separate free fatty acids (FFA) from triacylglycerols (TAGs) was examined. First, FFA/TAG solubility tests were completed (10-25 °C and 68-136 atm). The oil samples were separated using a FilmTec NF90 or a FilmTec BW30 membrane in a dead-end type cell. Within the range examined, the greatest solubility for oleic acid was at 25 °C and 136 atm. For soybean oil TAGs, the greatest solubility was at 20 _C and 136 atm. However, for the separation of the two components, 20 °C and 68 atm was best among the condition combinations examined. The solubility of oleic acid ranged from 0.294 to 0.455 mg/mL in subcritical carbon dioxide, while the solubility of triacylglycerols ranged from 0.066 to 0.139 mg/mL. The FilmTec BW30 membrane provided significantly better separation of FFAs from TAGs than did the NF90 membrane. Both membranes were selective for oleic acid, although the BW30 had greater selectivity for oleic acid (βoleic acid = 2.12, βTAGs = 0.24) than the NF90 membrane (βoleic acid = 1.26, βTAGs = 0.81). [ABSTRACT FROM AUTHOR]

Hash browns (HB) were fried (Teflon-coated pan, ∼180°C) with low-linolenic acid (LL-SBO) and creamy partially hydrogenated soybean oils (PH-SBO). High-performance size-exclusion chromatography of the oil extracted before heating indicated a relatively low polymer content (LL-SBO, 3.8%; PH-SBO, 1.6%), although the oil remaining in the pan after frying had a much greater polymer content (38.8%, LL-SBO; 17.5%, PH-SBO). The percentage of altered TAG in the LL-SBO sample (extracted from HB) was 34.4% after frying, whereas the PH-SBO had 33.2% altered TAG (as determined by supercritical fluid chromatography). In the LL-SBO pan-fried HB samples (not the extracted oil), 2-pentanone, hexanal, 2-hexenal, trans-2-heptenal, 2-pentylfuran, and trans-2-octenal were found, whereas the major volatile compounds in the HB fried with PH-SBO included hexanal, trans-2-hexenal, and trans-2-heptenal. Hexanal was the most abundant volatile compound in both HB samples (LL-SBO, 2.7 ppm; PH-SBO, 0.3 ppm). There were significant differences in the polymer content, hexanal content, p-anisidine values, and Foodoil sensor readings between LL-SBO and PH-SBO ( P<0.05). The PH-SBO sample was more stable than the LL-SBO sample. Moreover, the LL-SBO oil sample in the pan after frying had the greater increase in polymer content. [ABSTRACT FROM AUTHOR]

Background: Aging is associated with the accumulation of somatic mutations in post‐mitotic neurons. While this idea is not new, recent advances in single‐cell sequencing techniques have now made it possible to not only unequivocally prove that these mutations occur but also to estimate their occurrence rates. Here, we aimed to investigate whether somatic mutations are associated with Alzheimer's disease (AD) and gain insight into the potential pathophysiological consequences of such mutations in the brain. Method: Starting from the average annual somatic variation rate of healthy neurons, we modeled the likelihood of a gene being affected by somatic mutations over time, based on the transcribed length of that gene. Subsequently, we investigated the gene length distribution of genes that are affected by somatic mutations in AD brains and we analyzed differential mRNA expression data from eight AD brain areas, including pathway analysis. Result: Our model predicted that CNTNAP2, the largest gene in the human genome, has a 50% chance of having acquired at least one somatic mutation by the age of 65, which is in sharp contrast with average‐sized genes, in which there is only 1% chance of somatic mutations at 65. We also found that genes affected by somatic mutations are (much) longer than average and that larger genes are more likely to be reduced in their expression levels in AD‐vulnerable brain regions. Lastly, we found that these larger genes are predominantly expressed in neurons and are involved in synaptogenesis and synaptic adhesion, pathways that are predicted to be inhibited in AD based on the transcriptomic data. Conclusion: Our findings implicate somatic mutations in large genes as potential contributors to AD pathology through their effect on synaptic function. [ABSTRACT FROM AUTHOR]

An abstract of the article "Synthesis of (.+-.)-Amathaspiramide F (I) and Discovery of an Unusual Stereocontrolling Element for the [2,3]-Stevens Rearrangement" by Arash Soheili and Uttam K. Tambar re presented.

Unnatural cyclic amino acid derivatives are accessible through a palladium-catalyzed tandem allylic amination/Stevens rearrangement followed by ring-closing metathesis. [ABSTRACT FROM AUTHOR]