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  • Simultaneous Detection and Mutation Surveillance of SARS-CoV-2 and co-infections of multiple respiratory viruses by Rapid field-deployable sequencing.

    Bi, Chongwei; Ramos Mandujano, Gerardo; Tian, Yeteng; Hala, Sharif; Xu, Jinna; Mfarrej, Sara; Esteban, Concepcion Rodriguez; Delicado, Estrella Nuñez; Alofi, Fadwa S; Khogeer, Asim; Hashem, Anwar M; Almontashiri, Naif A M; Pain, Arnab; Izpisua Belmonte, Juan Carlos; Li, Mo (Med (New York, N.Y.), Elsevier BV, 2021-04-06) [Article]
    BackgroundStrategies for monitoring the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are crucial for combating the pandemic. Detection and mutation surveillance of SARS-CoV-2 and other respiratory viruses require separate and complex workflows that rely on highly-specialized facilities, personnel, and reagents. To date, no method can rapidly diagnose multiple viral infections and determine variants in a high-throughput manner.MethodsWe describe a method for multiplex isothermal amplification-based sequencing and real-time analysis of multiple viral genomes, termed NIRVANA. It can simultaneously detect SARS-CoV-2, influenza A, human adenovirus, and human coronavirus, and monitor mutations for up to 96 samples in real-time.FindingsNIRVANA showed high sensitivity and specificity for SARS-CoV-2 in 70 clinical samples with a detection limit of 20 viral RNA copies per μl of extracted nucleic acid. It also detected the influenza A co-infection in two samples. The variant analysis results of SARS-CoV-2 positive samples mirror the epidemiology of COVID-19. Additionally, NIRVANA could simultaneously detect SARS-CoV-2 and PMMoV (an omnipresent virus and water quality indicator) in municipal wastewater samples.ConclusionsNIRVANA provides high-confidence detection of both SARS-CoV-2 and other respiratory viruses and mutation surveillance of SARS-CoV-2 on the fly. We expect it to offer a promising solution for rapid field-deployable detection and mutational surveillance of pandemic viruses.FundingM.L. is supported by KAUST Office of Sponsored Research (BAS/1/1080-01). This work is supported by KAUST Competitive Research Grant (URF/1/3412-01-01, M.L. and J.C.I.B.) and Universidad Catolica San Antonio de Murcia (J.C.I.B.). A.M.H. is supported by Saudi Ministry of Education (project 436).
  • Simultaneous Detection and Mutation Surveillance of SARS-CoV-2 and co-infections of multiple respiratory viruses by Rapid field-deployable sequencing.

    Bi, Chongwei; Ramos Mandujano, Gerardo; Tian, Yeteng; Hala, Sharif; Xu, Jinna; Mfarrej, Sara; Esteban, Concepcion Rodriguez; Delicado, Estrella Nuñez; Alofi, Fadwa S; Khogeer, Asim; Hashem, Anwar M; Almontashiri, Naif A M; Pain, Arnab; Izpisua Belmonte, Juan Carlos; Li, Mo (Med (New York, N.Y.), Elsevier BV, 2021-04-06) [Article]
    BackgroundStrategies for monitoring the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are crucial for combating the pandemic. Detection and mutation surveillance of SARS-CoV-2 and other respiratory viruses require separate and complex workflows that rely on highly-specialized facilities, personnel, and reagents. To date, no method can rapidly diagnose multiple viral infections and determine variants in a high-throughput manner.MethodsWe describe a method for multiplex isothermal amplification-based sequencing and real-time analysis of multiple viral genomes, termed NIRVANA. It can simultaneously detect SARS-CoV-2, influenza A, human adenovirus, and human coronavirus, and monitor mutations for up to 96 samples in real-time.FindingsNIRVANA showed high sensitivity and specificity for SARS-CoV-2 in 70 clinical samples with a detection limit of 20 viral RNA copies per μl of extracted nucleic acid. It also detected the influenza A co-infection in two samples. The variant analysis results of SARS-CoV-2 positive samples mirror the epidemiology of COVID-19. Additionally, NIRVANA could simultaneously detect SARS-CoV-2 and PMMoV (an omnipresent virus and water quality indicator) in municipal wastewater samples.ConclusionsNIRVANA provides high-confidence detection of both SARS-CoV-2 and other respiratory viruses and mutation surveillance of SARS-CoV-2 on the fly. We expect it to offer a promising solution for rapid field-deployable detection and mutational surveillance of pandemic viruses.FundingM.L. is supported by KAUST Office of Sponsored Research (BAS/1/1080-01). This work is supported by KAUST Competitive Research Grant (URF/1/3412-01-01, M.L. and J.C.I.B.) and Universidad Catolica San Antonio de Murcia (J.C.I.B.). A.M.H. is supported by Saudi Ministry of Education (project 436).
  • Seasonal dynamics of natural Ostreococcus viral infection at the single cell level using VirusFISH.

    M Castillo, Yaiza; Forn, Irene; Yau, Sheree; Moran, Xose Anxelu G.; Alonso-Sáez, Laura; Arandia-Gorostidi, Néstor; Vaqué, Dolors; Sebastián, Marta (Environmental microbiology, Wiley, 2021-04-05) [Article]
    Ostreococcus is a cosmopolitan marine genus of phytoplankton found in mesotrophic and oligotrophic waters, and the smallest free-living eukaryotes known to date, with a cell diameter close to 1 μm. Ostreococcus has been extensively studied as a model system to investigate viral-host dynamics in culture, yet the impact of viruses in naturally occurring populations is largely unknown. Here, we used Virus Fluorescence in situ Hybridization (VirusFISH) to visualize and quantify viral-host dynamics in natural populations of Ostreococcus during a seasonal cycle in the central Cantabrian Sea (Southern Bay of Biscay). Ostreococcus were predominantly found during summer and autumn at surface and 50 m depth, in coastal, mid-shelf and shelf waters, representing up to 21% of the picoeukaryotic communities. Viral infection was only detected in surface waters, and its impact was variable but highest from May to July and November to December, when up to half of the population was infected. Metatranscriptomic data available from the mid-shelf station unveiled that the Ostreococcus population was dominated by the species O. lucimarinus. This work represents a proof of concept that the VirusFISH technique can be used to quantify the impact of viruses on targeted populations of key microbes from complex natural communities. This article is protected by copyright. All rights reserved.
  • Phylogenomics of Porites from the Arabian Peninsula.

    Terraneo, Tullia Isotta; Benzoni, Francesca; Arrigoni, Roberto; Baird, Andrew H; Mariappan, Kiruthiga; Forsman, Zac H; Wooster, Michael K; Bouwmeester, Jessica; Marshell, Alyssa; Berumen, Michael L. (Molecular phylogenetics and evolution, Elsevier BV, 2021-04-04) [Article]
    The advent of high throughput sequencing technologies provides an opportunity to resolve phylogenetic relationships among closely related species. By incorporating hundreds to thousands of unlinked loci and single nucleotide polymorphisms (SNPs), phylogenomic analyses have a far greater potential to resolve species boundaries than approaches that rely on only a few markers. Scleractinian taxa have proved challenging to identify using traditional morphological approaches and many groups lack an adequate set of molecular markers to investigate their phylogenies. Here, we examine the potential of Restriction-site Associated DNA sequencing (RADseq) to investigate phylogenetic relationships and species limits within the scleractinian coral genus Porites. A total of 126 colonies were collected from 16 localities in the seas surrounding the Arabian Peninsula and ascribed to 12 nominal and two unknown species based on their morphology. Reference mapping was used to retrieve and compare nearly complete mitochondrial genomes, ribosomal DNA, and histone loci. De novo assembly and reference mapping to the P. lobata coral transcriptome were compared and used to obtain thousands of genome-wide loci and SNPs. A suite of species discovery methods (phylogenetic, ordination, and clustering analyses) and species delimitation approaches (coalescent-based, species tree, and Bayesian Factor delimitation) suggested the presence of eight molecular lineages, one of which included six morphospecies. Our phylogenomic approach provided a fully supported phylogeny of Porites from the Arabian Peninsula, suggesting the power of RADseq data to solve the species delineation problem in this speciose coral genus.
  • Digital insights: bridging the phenotype-to-genotype divide

    McCabe, Matthew; Tester, Mark A. (Journal of Experimental Botany, Oxford University Press (OUP), 2021-04-02) [Article]
    The convergence of autonomous platforms for field-based phenotyping with advances in machine learning for big data analytics and rapid sequencing for genome description herald the promise of new insights and discoveries in the plant sciences. Han et al. (2021) leverage these emerging tools to navigate the challenging path from field-based mapping of phenotypic features to identifying specific genetic loci in the laboratory: in this case, loci responsible for regulating daily flowering time in lettuce. While their contribution neatly illustrates these exciting technological developments, it also highlights the work that remains to bridge these multidisciplinary fields to more fully deliver upon the promise of digital agriculture.
  • Identifying Novel Drug Targets by iDTPnd: A Case Study of Kinase Inhibitors.

    Naveed, Hammad; Reglin, Corinna; Schubert, Thomas; Gao, Xin; Arold, Stefan T.; Maitland, Michael L (Genomics, proteomics & bioinformatics, Elsevier BV, 2021-04-01) [Article]
    Current FDA-approved kinase inhibitors cause diverse adverse effects, some of which are due to the mechanism-independent effects of these drugs. Identifying these mechanism-independent interactions could improve drug safety and support drug repurposing. We have developed iDTPnd (integrated Drug Target Predictor with negative dataset), a computational approach for large-scale discovery of novel targets for known drugs. For a given drug, we construct a positive and a negative structural signature that captures the weakly conserved structural features of drug binding sites. To facilitate assessment of unintended targets, iDTPnd also provides a docking-based interaction score and its statistical significance. We were able to confirm the interaction of sorafenib, imatinib, dasatinib, sunitinib, and pazopanib with their known targets at a sensitivity and specificity of 52% and 55%, respectively. We have validated 10 predicted novel targets by using in vitro experiments. Our results suggest that proteins other than kinases, such as nuclear receptors, cytochrome P450, or MHC Class I molecules can also be physiologically relevant targets of kinase inhibitors. Our method is general and broadly applicable for the identification of protein-small molecule interactions, when sufficient drug-target 3D data are available. The code for constructing the structural signature is available at https://sfb.kaust.edu.sa/Documents/iDTP.zip.
  • Frequency-modulation Stimulated Raman Scattering microscopy with an Acousto-Optic Tunable Filter

    Grassi, Elisa (2021-04) [Thesis]
    Advisor: Liberale, Carlo
    Committee members: Habuchi, Satoshi; Hauser, Charlotte
    Stimulated Raman Scattering (SRS) is a Coherent Raman microscopy method that has been increasingly employed in recent years for highly-speci c, label-free, and high-speed bioimaging. Compared to a similar Coherent Raman method, the so-called Coherent Anti-Stokes Scattering (CARS) microscopy, it exhibits advantages such as the absence of nonresonant background (NRB) and the linearity of the signal intensity on the concentration of molecules of interest. However, SRS can be a ected by unwanted background signals that hinder the acquisition of an accurate Raman information. These unwanted signals are generated by parasitic e ects that are dif- cult to suppress in standard SRS setups. Here, I present a frequency-modulation (FM) SRS technique via an Acousto-Optic Tunable Filter (AOTF), describing its implementation on Vibra Lab setup and assessing its e ciency with imaging results. The FM technique provides a cancellation of the unwanted background signals, maintaining intact the SRS information. It is based on the weak spectral dependence of the parasitic e ects as compared to the high spectral speci city of the SRS signal. The proposed scheme presents a few advantages when compared with other solutions presented in the literature. In particular, it doesn't require a complex setup con guration, and it can be used seamlessly in a very broad range of the vibrational spectrum.
  • SEC6 exocyst subunit contributes to multiple steps of growth and development of Physcomitrella (Physcomitrium patens)

    Brejšková, Lucie; Hála, Michal; Rawat, Anamika; Soukupová, Hana; Cvrčková, Fatima; Charlot, Florence; Nogué, Fabien; Haluška, Samuel; Žárský, Viktor (Plant Journal, Wiley, 2021-04) [Article]
    Spatially directed cell division and expansion is important for plant growth and morphogenesis and relies on cooperation between the cytoskeleton and the secretory pathway. The phylogenetically conserved octameric complex exocyst mediates exocytotic vesicle tethering at the plasma membrane. Unlike other exocyst subunits of land plants, the core exocyst subunit SEC6 exists as a single paralog in Physcomitrium patens and Arabidopsis thaliana genomes. Arabidopsis SEC6 (AtSEC6) loss-of-function (LOF) mutation causes male gametophytic lethality. Our attempts to inactivate the P. patens SEC6 gene, PpSEC6, using targeted gene replacement produced two independent partial LOF (‘weak allele’) mutants via perturbation of the PpSEC6 gene locus. These mutants exhibited the same pleiotropic developmental defects: protonema with dominant chloronema stage; diminished caulonemal filament elongation rate; and failure in post-initiation gametophore development. Mutant gametophore buds, mostly initiated from chloronema cells, exhibited disordered cell file organization and cross-wall perforations, resulting in arrested development at the eight- to 10-cell stage. Complementation of both sec6 moss mutant lines by both PpSEC6 and AtSEC6 cDNA rescued gametophore development, including sexual organ differentiation. However, regular sporophyte formation and viable spore production were recovered only by the expression of PpSEC6, whereas the AtSEC6 complementants were only rarely fertile, indicating moss-specific SEC6 functions.
  • Genomes of the willow-galling sawflies Euura lappo and Eupontania aestiva (Hymenoptera: Tenthredinidae): a resource for research on ecological speciation, adaptation, and gall induction

    Michell, Craig; Wutke, Saskia; Aranda, Manuel; Nyman, Tommi (G3 Genes|Genomes|Genetics, Oxford University Press (OUP), 2021-03-31) [Article]
    Abstract Hymenoptera are a hyperdiverse insect order represented by over 153,000 different species. As many hymenopteran species perform various crucial roles for our environment, such as pollination, herbivory, and parasitism, they are of high economic and ecological importance. There are 99 hymenopteran genomes in the NCBI database, yet only five are representative of the paraphyletic suborder Symphyta (sawflies, woodwasps, and horntails), while the rest represent the suborder Apocrita (bees, wasps, and ants). Here, using a combination of 10X Genomics linked-read sequencing, Oxford Nanopore long-read technology, and Illumina short-read data, we assembled the genomes of two willow-galling sawflies (Hymenoptera: Tenthredinidae: Nematinae: Euurina): the bud-galling species Euura lappo and the leaf-galling species Eupontania aestiva. The final assembly for E. lappo is 259.85 Mbp in size, with a contig N50 of 209.0 kbp and a BUSCO score of 93.5%. The E. aestiva genome is 222.23 Mbp in size, with a contig N50 of 49.7 kbp and an 90.2% complete BUSCO score. De novo annotation of repetitive elements showed that 27.45% of the genome was composed of repetitive elements in E. lappo and 16.89% in E. aestiva, which is a marked increase compared to previously published hymenopteran genomes. The genomes presented here provide a resource for inferring phylogenetic relationships among basal hymenopterans, comparative studies on host-related genomic adaptation in plant-feeding insects, and research on the mechanisms of plant manipulation by gall-inducing insects.
  • Synergy and allostery in ligand binding by HIV-1 Nef

    Aldehaiman, Abdullah M; Momin, Afaque Ahmad Imtiyaz; Restouin, Audrey; Wang, Luyao; Shi, Xiaoli; Aljedani, Safia Salim Eid; Opi, Sandrine; Lugari, Adrien; Shahul Hameed, Umar F; Ponchon, Luc; Morelli, Xavier; Huang, Mingdong; Dumas, Christian; Collette, Yves; Arold, Stefan T. (Biochemical Journal, Portland Press Ltd., 2021-03-31) [Article]
    The Nef protein of human and simian immunodeficiency viruses boosts viral pathogenicity through its interactions with host cell proteins. By combining the polyvalency of its large unstructured regions with the binding selectivity and strength of its folded core domain, Nef can associate with many different host cell proteins, thereby disrupting their functions. For example, the combination of a linear proline-rich motif and hydrophobic core domain surface allows Nef to bind tightly and specifically to SH3 domains of Src family kinases. We investigated whether the interplay between Nef’s flexible regions and its core domain could allosterically influence ligand selection. We found that the flexible regions can associate with the core domain in different ways, producing distinct conformational states that alter the way in which Nef selects for SH3 domains and exposes some of its binding motifs. The ensuing crosstalk between ligands might promote functionally coherent Nef-bound protein ensembles by synergizing certain subsets of ligands while excluding others. We also combined proteomic and bioinformatics analyses to identify human proteins that select SH3 domains in the same way as Nef. We found that only 3% of clones from a whole-human fetal library displayed Nef-like SH3 selectivity. However, in most cases, this selectivity appears to be achieved by a canonical linear interaction rather than by a Nef-like “tertiary” interaction. Our analysis supports the contention that Nef’s mode of hijacking SH3 domains is a virus-specific adaptation with no or very few cellular counterparts. Thus, the Nef tertiary binding surface is a promising virus-specific drug target.
  • Microfluidic Integrated Organic Electrochemical Transistor with a Nanoporous Membrane for Amyloid-β Detection

    Koklu, Anil; Wustoni, Shofarul; Musteata, Valentina-Elena; Ohayon, David; Moser, Maximilian; McCulloch, Iain; Nunes, Suzana Pereira; Inal, Sahika (ACS Nano, American Chemical Society (ACS), 2021-03-30) [Article]
    Alzheimer’s disease (AD) is a neurodegenerative disorder associated with a severe loss in thinking, learning, and memory functions of the brain. To date, no specific treatment has been proven to cure AD, with the early diagnosis being vital for mitigating symptoms. A common pathological change found in AD-affected brains is the accumulation of a protein named amyloid-β (Aβ) into plaques. In this work, we developed a micron-scale organic electrochemical transistor (OECT) integrated with a microfluidic platform for the label-free detection of Aβ aggregates in human serum. The OECT channel–electrolyte interface was covered with a nanoporous membrane functionalized with Congo red (CR) molecules showing a strong affinity for Aβ aggregates. Each aggregate binding to the CR-membrane modulated the vertical ion flow toward the channel, changing the transistor characteristics. Thus, the device performance was not limited by the solution ionic strength nor did it rely on Faradaic reactions or conformational changes of bioreceptors. The high transconductance of the OECT, the precise porosity of the membrane, and the compactness endowed by the microfluidic enabled the Aβ aggregate detection over eight orders of magnitude wide concentration range (femtomolar–nanomolar) in 1 μL of human serum samples. We expanded the operation modes of our transistors using different channel materials and found that the accumulation-mode OECTs displayed the lowest power consumption and highest sensitivities. Ultimately, these robust, low-power, sensitive, and miniaturized microfluidic sensors helped to develop point-of-care tools for the early diagnosis of AD.
  • Organic J-Aggregate Nanodots with Enhanced Light Absorption and Near-Unity Fluorescence Quantum Yield

    Piwonski, Hubert Marek; Nozue, Shuho; Fujita, Hiroyuki; Michinobu, Tsuyoshi; Habuchi, Satoshi (Nano Letters, American Chemical Society (ACS), 2021-03-30) [Article]
    Development of biocompatible fluorophores with small size, bright fluorescence, and narrow spectrum translate directly into major advances in fluorescence imaging and related techniques. Here, we discover that a small donor–acceptor–donor-type organic molecule consisting of a carbazole (Cz) donor and benzothiazole (BT) acceptor (CzBTCz) assembles into quasi-crystalline J-aggregates upon a formation of ultrasmall nanoparticles. The 3.5 nm CzBTCz Jdots show a narrow absorption spectrum (fwhm = 27 nm), near-unity fluorescence quantum yield (ϕfl = 0.95), and enhanced peak molar extinction coefficient. The superior spectroscopic characteristics of the CzBTCz Jdots result in two orders of magnitude brighter photoluminescence of the Jdots compared with semiconductor quantum dots, which enables continuous single-Jdots imaging over a 1 h period. Comparison with structurally similar CzBT nanoparticles demonstrates a critical role played by the shape of CzBTCz on the formation of the Jdots. Our findings open an avenue for the development of a new class of fluorescent nanoparticles based on J-aggregate.
  • Novel hole-pillar spacer design for improved hydrodynamics and biofouling mitigation in membrane filtration.

    Qamar, Adnan; Kerdi, Sarah; Ali, Syed Muztuza; Shon, Ho Kyong; Vrouwenvelder, Johannes S.; Ghaffour, NorEddine (Scientific reports, Springer Science and Business Media LLC, 2021-03-27) [Article]
    Feed spacers are the critical components of any spiral-wound filtration module, dictating the filtration performance. Three spacer designs, namely a non-woven commercial spacer (varying filament cross-section), a symmetric pillar spacer, and a novel hole-pillar spacer (constant filament diameter) were studied using Direct Numerical Simulations (DNS), 3-D printed and subsequently experimentally tested in a lab-scale ultrafiltration set-up with high biofouling potential feed water at various feed pressures. Independent of the applied pressure, the novel hole-pillar spacer showed initially the lowest feed channel pressure drop, the lowest shear stress, and the highest permeate flux compared to the commercial and pillar spacers. Furthermore, less biofilm thickness development on membrane surface was visualized by Optical Coherent Tomography (OCT) imaging for the proposed hole-pillar spacer. At higher feed pressure, a thicker biofilm developed on membrane surface for all spacer designs explaining the stronger decrease in permeate flux at high pressure. The findings systematically demonstrated the role of various spacer designs and applied pressure on the performance of pre-treatment process, while identifying specific shear stress distribution guidelines for engineering a new spacer design in different filtration techniques.
  • Evidence of historical isolation and genetic structuring among broadnose sevengill sharks (Notorynchus cepedianus) from the world’s major oceanic regions

    Schmidt-Roach, Alicia C.J.; Bruels, Christine C.; Barnett, Adam; Miller, Adam D.; Sherman, Craig D.H.; Ebert, David A.; Schmidt-Roach, Sebastian; da Silva, Charlene; Wilke, Christopher G.; Thorburn, Craig; Mangel, Jeffrey C.; Ezcurra, Juan Manuel; Irigoyen, Alejo; Jaureguizar, Andrés Javier; Braccini, Matias; Alfaro-Shigueto, Joanna; Duffy, Clinton; Shivji, Mahmood S. (Reviews in Fish Biology and Fisheries, Springer Science and Business Media LLC, 2021-03-26) [Article]
    Cosmopolitan marine pelagic species display variable patterns of population connectivity among the world’s major oceans. While this information is crucial for informing management, information is lacking for many ecologically important species, including apex predators. In this study we examine patterns of genetic structure in the broadnose sevengill shark, Notorynchus cepedianus across its global distribution. We estimate patterns of connectivity among broadnose sevengill shark populations from three major oceanic regions (South Atlantic, Oceania and Eastern Pacific) by contrasting mitochondrial and nuclear DNA haplotype frequencies. We also produced time calibrated Bayesian Inference phylogenetic reconstructions to analyses global phylogeographic patterns and estimate divergence times among distinctive shark lineages. Our results demonstrate significant genetic differentiation among oceanic regions (ΦST = 0.9789, P < 0.0001) and a lack of genetic structuring within regions (ΦST = − 0.007; P = 0.479). Time calibrated Bayesian Inference phylogenetic reconstructions indicate that the observed patterns of genetic structure among oceanic regions are historical, with regional populations estimated to have diverged from a common ancestor during the early to mid-Pleistocene. Our results indicate significant genetic structuring and a lack of gene flow among broadnose sevengill shark populations from the South Atlantic, Oceania and Eastern Pacific regions. Evidence of deep lineage divergences coinciding with the early to mid-Pleistocene suggests historical glacial cycling has contributed to the vicariant divergence of broadnose sevengill shark populations from different ocean basins. These finding will help inform global management of broadnose sevengill shark populations, and provides new insights into historical and contemporary evolutionary processes shaping populations of this ecologically important apex predator.
  • Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking.

    Sanderson, Leslie E; Lanko, Kristina; Alsagob, Maysoon; AlMass, Rawan; Al-Ahmadi, Nada; Najafi, Maryam; Al-Muhaizea, Mohammad A; Alzaidan, Hamad; AlDhalaan, Hesham; Perenthaler, Elena; van der Linde, Herma C; Nikoncuk, Anita; Kühn, Nikolas A; Antony, Dinu; Owaidah, Tarek Mustafa; Raskin, Salmo; Vieira, Luana Gabriela Dalla Rosa; Mombach, Romulo; Ahangari, Najmeh; Silveira, Tainá Regina Damaceno; Ameziane, Najim; Rolfs, Arndt; Alharbi, Aljohara; Sabbagh, Raghda M; AlAhmadi, Khalid; Alawam, Bashayer; Ghebeh, Hazem; AlHargan, Aljouhra; Albader, Anoud A; Binhumaid, Faisal S; Goljan, Ewa; Monies, Dorota; Mustafa, Osama M; Aldosary, Mazhor; AlBakheet, Albandary; Alyounes, Banan; Almutairi, Faten; Al-Odaib, Ali; Aksoy, Durdane Bekar; Basak, A Nazli; Palvadeau, Robin; Trabzuni, Daniah; Rosenfeld, Jill A; Karimiani, Ehsan Ghayoor; Meyer, Brian F; Karakas, Bedri; Al-Mohanna, Futwan; Arold, Stefan T.; Colak, Dilek; Maroofian, Reza; Houlden, Henry; Bertoli-Avella, Aida M; Schmidts, Miriam; Barakat, Tahsin Stefan; van Ham, Tjakko J; Kaya, Namik (Brain : a journal of neurology, Oxford University Press (OUP), 2021-03-25) [Article]
    Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies in vacuolar protein sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation of macromolecules and organelles and are linked to human disease. VPS proteins function as part of complexes such as the homotypic fusion and vacuole protein sorting (HOPS) tethering complex, composed of VPS11, VPS16, VPS18, VPS33A, VPS39 and VPS41. The HOPS-specific subunit VPS41 has been reported to promote viability of dopaminergic neurons in Parkinson's disease but to date has not been linked to human disease. Here, we describe five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function.
  • The chromosome-scale reference genome of safflower (Carthamus tinctorius) provides insights into linoleic acid and flavonoid biosynthesis

    Wu, Zhihua; Liu, Hong; Zhan, Wei; Yu, Zhichao; Qin, Erdai; Liu, Shuo; Yang, Tiange; Xiang, Niyan; Kudrna, Dave; Chen, Yan; Lee, Seunghee; Li, Gang; Wing, Rod Anthony; Liu, Jiao; Xiong, Hairong; Xia, Chunjiao; Xing, Yongzhong; Zhang, Jianwei; Qin, Rui (Plant Biotechnology Journal, Wiley, 2021-03-25) [Article]
    Safflower (Carthamus tinctorius L.), a member of the Asteraceae, is a popular crop due to its high linoleic acid (LA) and flavonoid (such as hydroxysafflor yellow A) contents. Here, we report the first high-quality genome assembly (contig N50 of 21.23 Mb) for the 12 pseudochromosomes of safflower using single-molecule real-time sequencing, Hi-C mapping technologies, and a genetic linkage map. Phylogenomic analysis showed that safflower diverged from artichoke (Cynara cardunculus) and sunflower (Helianthus annuus) approximately 30.7 and 60.5 million years ago, respectively. Comparative genomic analyses revealed that uniquely expanded gene families in safflower were enriched for those predicted to be involved in lipid metabolism and transport and abscisic acid signaling. Notably, the fatty acid desaturase 2 (FAD2) and chalcone synthase (CHS) families, which function in the LA and flavonoid biosynthesis pathways, respectively, were expanded via tandem duplications in safflower. CarFAD2-12 was specifically expressed in seeds and was vital for high LA content in seeds, while tandemly duplicated CarFAD2 genes were upregulated in ovaries compared to CarFAD2-12, which indicates regulatory divergence of FAD2 in seeds and ovaries. CarCHS1, CarCHS4, and tandem-duplicated CarCHS5~CarCHS6, which were upregulated compared to other CarCHS members at early stages, contribute to the accumulation of major flavonoids in flowers. In addition, our data reveal multiple alternative splicing events in gene families related to fatty acid and flavonoid biosynthesis. Together, these results provide a high-quality reference genome and evolutionary insights into the molecular basis of fatty acid and flavonoid biosynthesis in safflower.
  • Real-Time Personal Fever Alert Monitoring by Wearable Detector Based on Thermoresponsive Hydrogel

    Wang, Wenbin; Wu, Chen; Zhu, Kai; Chen, Fang; Zhou, Jingjing; Shi, Yusuf; Zhang, Chenlin; Li, Renyuan; Wu, Mengchun; Zhuo, Sifei; Zhang, Hepeng; Wang, Peng (ACS Applied Polymer Materials, American Chemical Society (ACS), 2021-03-23) [Article]
    Quick fever screening at a mass scale is proven effective during a pandemic to single out the ones with suspected symptoms of infectious diseases. However, achieving affordable and real-time fever alert at an individual level, although more preferable, remains elusive. Herein, we report an inexpensive and highly sensitive fever detector, which possesses a sharp color transition temperature window tailor-tuned for fever screening. The sensing component of the detector is rationally designed thermoresponsive agarose@poly(N-isopropylacrylamide)-co-acrylamide hydrogel. The hydrogel turns from transparent to opaque white when its temperature is higher than its cloud point. As a proof of concept of its practical applicability, a wearable fever monitoring device was fabricated in the form of a wristband. When the wrist temperature is higher than the threshold of a human fever, the device shows a remarkable color change, alerting an elevated body temperature. The wearable detector provides a promising strategy for real-time fever alert monitoring and is capable of making contributions to inhibit the spread of infectious diseases during a pandemic.
  • Optimizing the energy recovery section in thermal desalination systems for improved thermodynamic, economic, and environmental performance

    Jamil, Muhammad Ahmad; Goraya, Talha S.; Ng, Kim Choon; Zubair, Syed M.; Xu, Ben Bin; Shahzad, Muhammad Wakil (International Communications in Heat and Mass Transfer, Elsevier BV, 2021-03-23) [Article]
    Integration of energy recovery section with thermal desalination systems improves their performance from thermodynamics, economics, and environmental viewpoints. This is because it significantly reduces input energy, heat transfer area, and capital cost requirements. Above all, the system outlet streams can achieve thermal equilibrium with the environment by supplying heat for useful preheating purposes thus reducing the environmental impacts. The plate heat exchangers are generally employed for this purpose as preheaters. The current paper presents a comprehensive investigation and optimization of these heat exchangers for thermal desalination systems applications. An experimentally validated numerical model employing Normalized Sensitivity Analysis and Genetic Algorithm based cost optimization is developed to investigate their performance at assorted operating conditions. The analysis showed that the heat transfer coefficient, pressure drop, and outlet water cost were improved by an increase in feed flow rate. However, with an increased flow rate, the comprehensive output parameter (h/ΔP) decreased due to the high degree increase in pressure drop. Moreover, an increase in the chevron angle reduced the heat transfer coefficient, pressure drop, and water cost. Finally, the optimization lowered the heat transfer area by ~79.5%, capital investment by ~62%, and the outlet cost of the cold stream by ~15.7%. The operational cost is increased due to the increased pressure drop but the overall impact is beneficial as Ctotal of equipment is reduced by ~52.7%.
  • Moonlighting adenylyl cyclases in plants: an Arabidopsis thaliana 9-cis-epoxycarotenoid dioxygenase as point in case

    Al-Younis, Inas; Wong, Aloysius Tze; Moosa, Basem; Kwiatkowski, Mateusz; Jaworski, Krzysztof; Gehring, Christoph A (Cold Spring Harbor Laboratory, 2021-03-23) [Preprint]
    Adenylyl cyclases (ACs) and their catalytic product cAMP are regulatory components of plant responses. AC domains are intrinsic components of complex molecules with multiple functions, some of which are co-regulated by cAMP. Here we used an amino acid search motif based on annotated ACs in organisms across species to identify 12 unique Arabidopsis thaliana candidate ACs, four of which have a role in the biosynthesis of the stress hormone abscisic acid (ABA). One of these, the 9-cis-epoxycarotenoid dioxygenase (NCED3, At3g14440), was identified by sequence and structural analysis as a putative AC and then tested experimentally for activity. We show that an NCED3 AC fragment can complement an AC deficient E. coli mutant and this rescue is nullified when key amino acids in the AC motif are mutated. AC activity was also confirmed by tandem liquid chromatography mass spectrometry (LC-MS/MS). Our results are consistent with a moonlighting role for mononucleotide cyclases in multi-domain proteins that have at least one other distinct molecular function such as catalysis or ion channel activation and promise to yield new insights into tuning mechanisms of ABA dependent plant responses. Finally, our search method can also be applied to discover ACs in other species including Homo sapiens.
  • MYH1 is a candidate gene for recurrent rhabdomyolysis in humans

    Alsaif, Hessa S.; Alshehri, Ali; Sulaiman, Raashda A.; Al-Hindi, Hindi; Guzmán-Vega, Francisco J.; Arold, Stefan T.; Alkuraya, Fowzan S. (American Journal of Medical Genetics Part A, Wiley, 2021-03-23) [Article]
    Rhabdomyolysis is a serious medical condition characterized by muscle injury, and there are recognized genetic causes especially in recurrent forms. The majority of these cases, however, remain unexplained. Here, we describe a patient with recurrent rhabdomyolysis in whom extensive clinical testing failed to identify a likely etiology. Whole-exome sequencing revealed a novel missense variant in MYH1, which encodes a major adult muscle fiber protein. Structural biology analysis revealed that the mutated residue is extremely well conserved and is located in the actin binding cleft. Furthermore, immediately adjacent mutations in that cleft in other myosins are pathogenic in humans. Our results are consistent with the finding that MYH1 is mutated in rhabdomyolysis in horses and suggest that this gene should be investigated in cases with recurrent rhabdomyolysis.

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