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157. Bi-allelic variants in OGDHL cause a neurodevelopmental spectrum disease featuring epilepsy, hearing loss, visual impairment, and ataxia

Author

Yap, Zheng Yie, Efthymiou, Stephanie, Seiffert, Simone, Parra, Karen Vargas, Lee, Sukyeong, Nasca, Alessia, Maroofian, Reza, Schrauwen, Isabelle, Pendziwiat, Manuela, Jung, Sunhee, Bhoj, Elizabeth, Striano, Pasquale, Mankad, Kshitij, Vona, Barbara, Cuddapah, Sanmati, Wagner, Anja, Alvi, Javeria Raza, Davoudi-Dehaghani, Elham, Fallah, Mohammad-Sadegh, Gannavarapu, Srinitya, Lamperti, Costanza, Legati, Andrea, Murtaza, Bibi Nazia, Nadeem, Muhammad Shahid, Rehman, Mujaddad Ur, Saeidi, Kolsoum, Salpietro, Vincenzo, von Spiczak, Sarah, Sandoval, Abigail, Zeinali, Sirous, Zeviani, Massimo, Reich, Adi, Group, SYNaPS Study, Genomics, University of Washington Center for Mendelian, Jang, Cholsoon, Helbig, Ingo, Barakat, Tahsin Stefan, Ghezzi, Daniele, Leal, Suzanne M, Weber, Yvonne, Houlden, Henry, and Yoon, Wan Hee

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Clinical Research, Brain Disorders, Neurosciences, Neurodegenerative, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Neurological, Alleles, Animals, Ataxia, Cells, Cultured, Child, Cohort Studies, DNA Mutational Analysis, Drosophila melanogaster, Epilepsy, Family Health, Female, Fibroblasts, Hearing Loss, Humans, Ketoglutarate Dehydrogenase Complex, Male, Mutation, Neurodevelopmental Disorders, RNA Splicing, Vision Disorders, SYNaPS Study Group, University of Washington Center for Mendelian Genomics, CRISPR-Cas9 gene editing, DEE, Drosophila, OGDHL, bi-allelic, developmental and epileptic encephalopathy, exome sequencing, mitochondria, neurodevelopmental disease, α-ketoglutarate, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to the brain in humans. Here, we report nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum. The variants include three homozygous missense variants (p.Pro852Ala, p.Arg244Trp, and p.Arg299Gly), three compound heterozygous single-nucleotide variants (p.Arg673Gln/p.Val488Val, p.Phe734Ser/p.Ala327Val, and p.Trp220Cys/p.Asp491Val), one homozygous frameshift variant (p.Cys553Leufs∗16), and one homozygous stop-gain variant (p.Arg440Ter). To support the pathogenicity of the variants, we developed a novel CRISPR-Cas9-mediated tissue-specific knockout with cDNA rescue system for dOgdh, the Drosophila ortholog of human OGDHL. Pan-neuronal knockout of dOgdh led to developmental lethality as well as defects in Krebs cycle metabolism, which was fully rescued by expression of wild-type dOgdh. Studies using the Drosophila system indicate that p.Arg673Gln, p.Phe734Ser, and p.Arg299Gly are severe loss-of-function alleles, leading to developmental lethality, whereas p.Pro852Ala, p.Ala327Val, p.Trp220Cys, p.Asp491Val, and p.Arg244Trp are hypomorphic alleles, causing behavioral defects. Transcript analysis from fibroblasts obtained from the individual carrying the synonymous variant (c.1464T>C [p.Val488Val]) in family 2 showed that the synonymous variant affects splicing of exon 11 in OGDHL. Human neuronal cells with OGDHL knockout exhibited defects in mitochondrial respiration, indicating the essential role of OGDHL in mitochondrial metabolism in humans. Together, our data establish that the bi-allelic variants in OGDHL are pathogenic, leading to a Mendelian neurodevelopmental disease in humans.

Published
2021

160. Quantum Anomalous Hall Effect in Magnetic Doped Topological Insulators and Ferromagnetic Spin-Gapless Semiconductors -- A Perspective Review

Author

Nadeem, Muhammad, Hamilton, Alex R., Fuhrer, Michael S., and Wang, Xiaolin

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Materials Science
Abstract

Quantum anomalous Hall effect, with a trademark of dissipationless chiral edge states for electronics/spintronics transport applications, can be realized in materials with large spin-orbit coupling and strong intrinsic magnetization. After Haldane seminal proposal, several models have been presented to control/enhance the spin-orbit coupling and intrinsic magnetic exchange interaction. After brief introduction of Haldane model for spineless fermions, following three fundamental quantum anomalous Hall models are discussed in this perspective review: (i) low-energy effective four band model for magnetic-doped topological insulator (Bi,Sb)2Te3 thin films, (ii) four band tight-binding model for graphene with magnetic adatoms, and (iii) two (three) band spinfull tight-binding model for ferromagnetic spin-gapless semiconductors with honeycomb (kagome) lattice where ground state is intrinsically ferromagnetic. These models cover two-dimensional Dirac materials hosting spinless, spinful and spin-degenerate Dirac points where various mass terms open a band gap and lead to quantum anomalous Hall effect. With emphasize on the topological phase transition driven by ferromagnetic exchange interaction and its interplay with spin-orbit-coupling, we discuss various symmetry constraints on the nature of mass term and the materialization of these models. We hope this study will shed light on the fundamental theoretical perspectives of quantum anomalous Hall materials.

Published
2020
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161. Overcoming Boltzmann's Tyranny in a Transistor via the Topological Quantum Field Effect

Author

Nadeem, Muhammad, Di Bernardo, Iolanda, Wang, Xiaolin, Fuhrer, Michael S., and Culcer, Dimitrie

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

The sub-threshold swing is the fundamental critical parameter determining the operation of a transistor in low-power applications such as switches. It determines the fraction of dissipation due to the gate capacitance used for turning the device on and off, and in a conventional transistor it is limited by Boltzmann's tyranny to kTln(10)/q, or 60 mV per decade. Here, we demonstrate that the sub-threshold swing of a topological transistor, in which conduction is enabled by a topological phase transition via electric field switching, can be sizably reduced in a non-interacting system by modulating the Rashba spin-orbit interaction via a top-gate electric field. We refer to this as the Topological Quantum Field Effect and to the transistor as a Topological Quantum Field Effect transistor (TQFET). By developing a general theoretical framework for quantum spin Hall materials with honeycomb lattices we explicitly show that the Rashba interaction can reduce the sub-threshold swing by more than 25% compared to Boltzmann's limit in currently available materials, but without any fundamental lower bound, a discovery that can guide future materials design and steer the engineering of topological quantum devices., Comment: 14 pages, 4 figures, 1 table

Published
2020
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167. Phytohormones as Stress Mitigator in Plants

Author

Ul Abidin, Zain, Mahmood, Athar, Bibi, Safura, Mansoor Javaid, Muhammad, Zia, Muhammad Anjum, Saad Ullah, Muhammad, Azeem, Muhammad, Nadeem, Muhammad Ather, Khan, Bilal Ahmad, and Hasanuzzaman, Mirza, editor

Published
2023
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174. Flexible Electrically Conductive Elastomers

Author

Ali, Azam, Nadeem, Muhammad Faisal, Khan, Muhammad Zaman, Venkataraman, Mohanapriya, Perveen, Sajida, Palanisamy, Sundaramoorthy, Militký, Jiří, Öchsner, Andreas, Series Editor, da Silva, Lucas F. M., Series Editor, Altenbach, Holm, Series Editor, Militký, Jiří, editor, and Venkataraman, Mohanapriya, editor

Published
2023
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177. Nutrient Management Under Changing Climate

Author

Anwar-ul-Haq, Muhammad, Mehmood, Muhammad Tayyab, Alisha, Seed, Saba, Haider, Sharjeel, Awais, Muhammad, Nadeem, Muhammad, Mubeen, Muhammad, Iftikhar, Irfan, Jatoi, Wajid Nasim, editor, Mubeen, Muhammad, editor, Hashmi, Muhammad Zaffar, editor, Ali, Shaukat, editor, Fahad, Shah, editor, and Mahmood, Khalid, editor

Published
2023
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188. Comparative evaluation of chemically and green synthesized zinc oxide nanoparticles: their in vitro antioxidant, antimicrobial, cytotoxic and anticancer potential towards HepG2 cell line

Author

Ashraf, Hajra, Meer, Bisma, Iqbal, Junaid, Ali, Joham Sarfraz, Andleeb, Anisa, Butt, Hira, Zia, Muhammad, Mehmood, Azra, Nadeem, Muhammad, Drouet, Samantha, Blondeau, Jean-Philippe, Giglioli-Guivarc’h, Nathalie, Liu, Chunzhao, Hano, Christophe, and Abbasi, Bilal Haider

Published
2023
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193. Chitosan nanoparticles loaded with mesosulfuron methyl and mesosulfuron methyl + florasulam + MCPA isooctyl to manage weeds of wheat (Triticum aestivum L.)

Author

Khan Bilal Ahmad, Nadeem Muhammad Ather, Iqbal Mudassar, Yaqoob Neelam, Javaid Muhammad Mansoor, Maqbool Rizwan, Elnaggar Nehal, and Oraby Hesham

Subjects
chitosan nanoherbicides, weed management, chlorophyll content, weed fresh and dry biomass, wheat (triticum aestivum l.), Chemistry, QD1-999
Abstract

Nanoherbicides are articulated by empowering the potential of nanotechnology for the efficacious delivery of chemical or biological herbicides with the aid of nanomaterial‐based herbicide combinations. Therefore, the goal of this work was to investigate the chitosan nanoparticles loaded with mesosulfuron methyl and mesosulfuron methyl + florasulam + (2-methyl-4-chlorophenoxyacetic acid) MCPA isooctyl herbicides as a possible environmentally benign substitute to manage weeds in wheat. Due to intriguing characteristics including biocompatibility, low allergenicity, biodegradability, and nontoxicity, chitosan biopolymers as sustainable chitin derivatives have received intense scrutiny in the biomedical business. The manufactured nanoparticles were characterized by using ultraviolet absorbance, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). The average particle size as revealed by SEM was 40–70 nm in a cluster form with the porous structure. The maximum absorption peaks of both nanoparticles of mesosulfuron methyl and mesosulfuron methyl + florasulam + MCPA isooctyl were 330 and 360 nm. The FT-IR analysis showed an intensive peak at 2θ value of 30.55° for mesosulfuron methyl and 32.79° for mesosulfuron methyl + florasula + MCPA isooctyl, which correspond to the 78 and 198 planes of the anatase phase, respectively. The nanoparticles were sprayed at the third to fourth leaf stages of the targeted weeds. Seven different doses were applied. A total of 100% mortality and visual injury were caused by the chitosan-based nanoparticles of both herbicides at the recommended dose of standard herbicide. The 5-fold lower dose showed the minimum chlorophyll content (5.75%), plant height (2.35 cm), fresh biomass (1.08 g), and dry biomass (0.33 g) of a weed mixture. For the same traits, the herbicide nanoparticles at 10-fold lower dose of commercial herbicides exhibited a similar effect as the recommended dose. Nanoherbicides could recuperate the conventional herbicide effectiveness by enhancing the stability and reducing the toxicity.

Published
2023
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194. Inequalities of Chebyshev-P\'olya-Szeg\'o Type via Generalized Proportional Fractional Integral Operators

Author

Butt, Saad Ihsan, Akdemir, Ahmet Ocak, Ekinci, Alper, and Nadeem, Muhammad

Subjects
Mathematics - General Mathematics
Abstract

This study is an example of a solid connection between fractional analysis and inequality theory, and includes new inequalities of the P\'{o}lya-Szeg% \"{o}-Chebyshev type obtained with the help of Generalized Proportional Fractional integral operators. The results have been performed by using Generalized Proportional Fractional integral operators, some classical inequalities such as AM-GM inequality, Cauchy-Schwarz inequality and Taylor series expansion of exponential function. The findings give new approaches to some types of inequalities that have involving the product of two functions in inequality theory.

Published
2020

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