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Barbara J. Meyer: 2018 Thomas Hunt Morgan Medal

GENETICS 2019年第1期211卷 1-3页

作者： Haloupek, Nicole Genet Soc Amer Rockville MD 20852 USA

Meyer’s work has revealed mechanisms of sex determination and dosage compensation in Caenorhabditis elegans that continue to serve as the foundation of diverse areas of study on chromosome structure and function today, nearly 40 years after she began her work on the topic. [...]Meyer did not start her academic career with plans to become a biologist. [...]the DCC shares 4 of its 10 subunits with condensin complexes involved in mitosis and meiosis (Chuang et al. 1994; Lieb et al. 1998; Mets and Meyer 2009), while other DCC subunits do double-duty with complexes involved in histone methylation (Pferdehirt et al. 2011; Brejc et al. 2017). Pferdehirt, R. R., W. S. Kruesi, and B. J. Meyer, 2011 An MLL/ COMPASS subunit functions in the C. elegans dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression.

关键词： Laboratories Dosage compensation Chromosomes Methylation Gene regulation Genetics Transcription Researchers Sex determination Compensation Dosage Nematodes Sexes Condensin Gene expression Careers Mitosis Medical research Meiosis Worms structure-function relationships

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Degeneracy in hippocampal physiology and plasticity

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HIPPOCAMPUS 2019年第10期29卷 980-1022页

作者： Rathour, Rahul K. Narayanan, Rishikesh Indian Inst Sci Cellular Neurophysiol Lab Mol Biophys Unit Bangalore Karnataka India

Degeneracy, defined as the ability of structurally disparate elements to perform analogous function, has largely been assessed from the perspective of maintaining robustness of physiology or plasticity. How does the framework of degeneracy assimilate into an encoding system where the ability to change is an essential ingredient for storing new incoming information? Could degeneracy maintain the balance between the apparently contradictory goals of the need to change for encoding and the need to resist change towards maintaining homeostasis? In this review, we explore these fundamental questions with the mammalian hippocampus as an example encoding system. We systematically catalog lines of evidence, spanning multiple scales of analysis that point to the expression of degeneracy in hippocampal physiology and plasticity. We assess the potential of degeneracy as a framework to achieve the conjoint goals of encoding and homeostasis without cross-interferences. We postulate that biological complexity, involving interactions among the numerous parameters spanning different scales of analysis, could establish disparate routes towards accomplishing these conjoint goals. These disparate routes then provide several degrees of freedom to the encoding-homeostasis system in accomplishing its tasks in an input- and state-dependent manner. Finally, the expression of degeneracy spanning multiple scales offers an ideal reconciliation to several outstanding controversies, through the recognition that the seemingly contradictory disparate observations are merely alternate routes that the system might recruit towards accomplishment of its goals.

关键词： Degeneracy learning memory encoding homeostasis causality reductionism holism structure-function relationships variability compensation

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structure-based functional analysis of BRCA1 RING domain variants: Concordance of computational mutagenesis, experimental assay, and clinical data

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BIOPHYSICAL CHEMISTRY 2020年 266卷 106442-106442页

作者： Masso, Majid Bansal, Anirudh Bansal, Arnav Henderson, Andrea George Mason Univ Coll Sci Sch Syst Biol 10900 Univ Blvd MS 5B3 Manassas VA 20110 USA

A significant impediment to the improvement of clinical outcomes in treating breast and ovarian cancers rests with the lack of available interpretations for BRCA1 variants of unknown significance. Two research groups recently implemented large-scale functional assays for quantifying effects of single missense mutations on homology-directed DNA repair activity of BRCA1 variants, which is critical for tumor suppression and strongly correlates with cancer risk, and their results are significantly concordant with each other as well as with known pathogenic and benign variant clinical data. In this work, we implemented an established computational mutagenesis procedure to characterize structural impacts of single residue replacements to the BRCA1 RING domain. The computational data showed similarly strong concordance with known clinical data as well as with experimental data from both functional assays. Predictions made by models trained on our computational data offer a complementary and orthogonal approach for classifying all remaining unexplored BRCA1 RING domain variants.

关键词： structure-function relationships Computational mutagenesis Variants Homology-directed DNA repair Machine learning Prediction

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Biochemical characterization of mouse D-aspartate oxidase

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BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 2020年第10期1868卷 140472-140472页

作者： Puggioni, Vincenzo Savinelli, Antonio Miceli, Matteo Molla, Gianluca Pollegioni, Loredano Sacchi, Silvia Univ Insubria Dipartimento Biotecnol & Sci Vita Prot Factory 20 Via JH Dunant 3 I-21100 Varese Italy Int Res Ctr D Amino Acids DAAIR Via Lepetit 34 I-21040 Gerenscuto VA Italy

D-amino acids research field has recently gained an increased interest since these atypical molecules have been discovered to play a plethora of different roles. In the mammalian central nervous system, D-aspartate (D-Asp) is critically involved in the regulation of glutamatergic neurotransmission by acting as an agonist of NMDA receptor. Accordingly, alterations in its metabolism have been related to different pathologies. D-Asp shows a peculiar temporal pattern of emergence during ontogenesis and soon after birth its brain levels are strictly regulated by the catabolic enzyme D-aspartate oxidase (DASPO), a FAD-dependent oxidase. Rodents have been widely used as in vivo models for deciphering molecular mechanisms and for testing novel therapeutic targets and drugs, but human targets can significantly differ. Based on these considerations, here we investigated the structural and functional properties of the mouse DASPO, in particular kinetic properties, ligand and flavin binding, oligomerization state and protein stability. We compared the obtained findings with those of the human enzyme (80% sequence identity) highlighting a different oligomeric state and a lower activity for the mouse DASPO, which apoprotein species exists in solution in two forms differing in FAD affinity. The features that distinguish mouse and human DASPO suggest that this flavoenzyme might control in a distinct way the brain D-Asp levels in different organisms.

关键词： Flavoproteins D-amino acids structure-function relationships Protein stability Cofactor binding

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Characterization and antioxidant activities of polysaccharides from thirteen boletus mushrooms

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 2018年第0期113卷 1-7页

作者： Zhang, Lan Hu, Yu Duan, Xiaoyu Tang, Tingting Shen, Yingbin Hu, Bin Liu, Aiping Chen, Hong Li, Cheng Liu, Yuntao Sichuan Agr Univ Coll Food Sci 46 Xinkang Rd Yaan 625014 Sichuan Peoples R China Jinan Univ Dept Food Sci & Engn Guangzhou 510632 Guangdong Peoples R China

Water-soluble polysaccharides were extracted from the caps and stipes of thirteen boletus mushrooms representing five different species collected in Southwest China. Investigations of their structures and antioxidant activities allowed an evaluation of structure-function relationships. The polysaccharides were composed mainly of the monosaccharides arabinose, xylose, mannose, glucose and galactose. Most samples displayed a broad molecular weight range, with significant differences observed between the molecular weight ranges of the polysaccharides from the caps and the stipes. FT-IR spectral analysis of the polysaccharides revealed that most of polysaccharides from boletus mushrooms (except Boletus edulis) contained a pyranose ring. The antioxidant activities of the polysaccharides in stipes showed a significant correlation with their monosaccharide composition, and were also related to their molecular weight and anomeric configuration. Suillellus luridus collected in Pingwu, Mianyang, Sichuan, China had remarkably superior antioxidant activity and might be developed as a natural antioxidant. (C) 2018 Elsevier B.V. All rights reserved.

关键词： Boletus mushrooms Polysaccharides Antioxidant activities structure-function relationships

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Discerning the Redox-Dependent Electronic and Interfacial structures in Electroactive Self-Assembled Monolayers

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2018年第42期140卷 13672-13679页

作者： Wong, Raymond A. Yokota, Yasuyuki Wakisaka, Mitsuru Inukai, Junji Kim, Yousoo RIKEN Surface & Interface Sci Lab 2-1 Hirosawa Wako Saitama 3510198 Japan Toyama Prefectural Univ Grad Sch Engn 5180 Kurokawa Imizu Toyama 9390398 Japan Univ Yamanashi Clean Energy Res Ctr 4 Takeda Kofu Yamanashi 4008510 Japan

We explore the redox-dependent electronic and structural changes of ferrocene-terminated self-assembled monolayers (Fc SAMs) immersed in aqueous solution. By exploiting X-ray and ultraviolet photoelectron spectroscopy combined with an electrochemical cell (EC-XPS/UPS), we can electrochemically control the Fc SAMs and spectroscopically probe the induced changes with the ferrocene/ferrocenium (Fc/Fc(+)) redox center (Fe oxidation state), formation of 1:1 Fc(+)-ClO4- ion pairs, molecular orientation, and monolayer thickness. We further find the insignificant involvement of interfacial water in the Fc SAMs irrespective of redox state. Electrolyte dependencies could be identified with 0.1 M NaClO4 and HClO4 when probing partially oxidized Fc/Fc(+) SAMs. Corroborating the occurrence of electrochemically induced oxidation, EC-UPS shows that oxidation to Fc(+) is accompanied by a shift of the highest occupied molecular orbital toward higher binding energy. The oxidation to Fc(+) is also met with an increase in work function ascribed to the induced negative interfacial dipole caused by the presence of Fc(+)-ClO4- ion pairs along with a contribution from the reorientation of the Fc(+) SAMs. The reversibility of our observations is confirmed upon conversion from Fc(+) back to the neutral Fc. The approach shown here is beneficial for a broad range of redox-responsive systems to aid in the elucidation of structure-function relationships.

关键词： Work function Vocational Rehabilitation Oxidation Fc structure-function relationships molecular orientation self-assembled monolayers Ultraviolet Photoelectron Spectroscopy Ion pairs

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Assessing the functional Response to Streamside Fencing of Pastoral Waikato Streams, New Zealand

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WATER 2019年第7期11卷 1347-1347页

作者： Doehring, Katharina Clapcott, Joanne E. Young, Roger G. Cawthron Inst 98 Halifax St East Nelson 7010 New Zealand

In New Zealand, streamside fencing is a well-recognised restoration technique for pastoral waterways. However, the response of stream ecosystem function to fencing is not well quantified. We measured the response to fencing of eight variables describing ecosystem function and 11 variables describing physical habitat and water quality at 11 paired stream sites (fenced and unfenced) over a 30-year timespan. We hypothesised that (1) fencing would improve the state of stream ecosystem health as described by physical, water quality and functional indicators due to riparian re-establishment and (2) time since fencing would increase the degree of change from impacted to less-impacted as described by physical, water quality and functional indicators. We observed high site-to-site variability in both physical and functional metrics. Stream shade was the only measure that showed a significant difference between treatments with higher levels of shade at fenced than unfenced sites. Cotton tensile-strength loss was the only functional measurement that indicated a response to fencing and increased over time since treatment within fenced sites. Our results suggest that stream restoration by fencing follows a complex pathway, over a space-for-time continuum, illustrating the overarching catchment influence at a reach scale. Small-scale (less than 2% of the upstream catchment area) efforts to fence the riparian zones of streams appear to have little effect on ecosystem function. We suggest that repeated measures of structural and functional indicators of ecosystem health are needed to inform robust assessments of stream restoration.

关键词： functional indicators stream restoration riparian vegetation fencing cotton tensile-strength loss wood decay ecosystem metabolism organic matter transport catchment restoration structure-function relationships

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Hydraulic and mechanical dysfunction of Norway spruce sapwood due to extreme summer drought in Scandinavia

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FOREST ECOLOGY AND MANAGEMENT 2018年 409卷 527-540页

作者： Rosner, Sabine Gierlinger, Notburga Klepsch, Matthias Karlsson, Bo Evans, Rob Lundqvist, Sven-Olof Svetlik, Jan Borja, Isabella Dalsgaard, Lise Andreassen, Kjell Solberg, Svein Jansen, Steven BOKU Vienna Inst Bot Gregor Mendel Str 33 A-1180 Vienna Austria BOKU Vienna Inst Biophys Muthgasse 11 A-1190 Vienna Austria Ulm Univ Inst Systemat Bot & Ecol Albert Einstein Allee 11 D-89081 Ulm Germany Forestry Res Inst Sweden Skogforsk S-26890 Ekebo Sweden St1viScan Pty Ltd 8 Dobell Pl Doncaster East Vic 3109 Australia Univ Melbourne Sch Ecosyst & Forest Sci 500 Yarra Blvd Burnley Vic 3121 Australia IIC AB Rosenlundsgatan 48B SE-11863 Stockholm Sweden RISE INNVENTIA AB Drottning Kristinas Vag 61 B SE-11428 Stockholm Sweden Mendel Univ Brno Ctr MendelGlobe Global Climate Change & Managed E Zemedelska 3 Brno 61300 Czech Republic Norwegian Inst Bioecon Res NIBIO POB 115 NO-1431 As Norway

Projected climate change scenarios such as frequently occurring dry summer spells are an enormous threat to the health of boreal conifer forests. We identified visible features indicating wood with tracheids predisposed for hydraulic and mechanical dysfunction in Norway spruce, suggest why this is formed during severe summer drought and hypothesised on mechanism that would cause tracheid collapse and stem cracks. Trees from southern Sweden that showed signs of severe reaction to drought, i.e. stem cracks along the trunk, were compared to healthy, undamaged trees. Rings investigated included those formed in 2006, a year with an extremely dry summer season in the study region. In southern Norway, we investigated trees with and without drought-induced top dieback symptoms. We analysed anatomical features such as tracheid lumen diameter, thickness of cell wall and its various layers (S1, S2 and S3), applied Raman imaging in order to get information on the lignin distribution in the cell wall and the compound middle lamellae and performed hydraulic flow and shrinkage experiments. Although tracheids in annual rings with signs of collapse had higher tangential lumen diameters than those in "normal" annual rings, we conclude that collapse of tracheid walls depends mainly on wall thickness, which is genetically determined to a large extent. Spruce trees that produce earlywood with extremely thin cell walls can develop wall collapse and internal cracks under the impact of dry spells. We also present a new diagnostic tool for detecting individuals that are prone to cell wall collapse and stem cracks: Lucid bands, i.e. bands in the fresh sapwood with very thin cell walls and inhomogeneous lignin distribution in the S-layers and the compound middle lamellae that lost their hydraulic function due to periods of severe summer drought. The detection of genotypes with lucid bands could be useful for an early selection against individuals that are prone to stem cracks under the impact

关键词： Conduit wall reinforcement Drought Global warming Hydraulic failure Norway spruce Picea abies structure-function relationships Wall collapse Wood cracks

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The N terminus and transmembrane segment S1 of Kv1.5 can coassemble with the rest of the channel independently of the S1-S2 linkage

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JOURNAL OF BIOLOGICAL CHEMISTRY 2018年第40期293卷 15347-15358页

作者： Lamothe, Shawn M. Hogan-Cann, Aja E. Li, Wentao Guo, Jun Yang, Tonghua Tschirhart, Jared N. Zhang, Shetuan Queens Univ Dept Biomed & Mol Sci 18 Stuart St Kingston ON K7L 3N6 Canada

The voltage-gated potassium channel Kv1.5 belongs to the Shaker superfamily. Kv1.5 is composed of four subunits, each comprising 613 amino acids, which make up the N terminus, six transmembrane segments (S1-S6), and the C terminus. We recently demonstrated that, in HEK cells, extracellularly applied proteinase K (PK) cleaves Kv1.5 channels at a single site in the S1-S2 linker. This cleavage separates Kv1.5 into an N-fragment (N terminus to S1) and a C-fragment (S2 to C terminus). Interestingly, the cleavage does not impair channel function. Here, we investigated the role of the N terminus and S1 in Kv1.5 expression and function by creating plasmids encoding various fragments, including those that mimic PK-cleaved products. Our results disclosed that although expression of the pore-containing fragment (Frag(304-613)) alone could not produce current, coexpression with Frag(1-303) generated a functional channel. Immunofluorescence and biotinylation analyses uncovered that Frag(1-303) was required for Frag(304-613) to traffic to the plasma membrane. Biochemical analysis revealed that the two fragments interacted throughout channel trafficking and maturation. In Frag(1-303)+(304-613)-coassembled channels, which lack a covalent linkage between S1 and S2, amino acid residues 1-209 were important for association with Frag(304-613), and residues 210-303 were necessary for mediating trafficking of coassembled channels to the plasma membrane. We conclude that the N terminus and S1 of Kv1.5 can attract and coassemble with the rest of the channel (i.e. Frag(304-613)) to form a functional channel independently of the S1-S2 linkage.

关键词： electrophysiology structure-function relationships voltage-gated potassium channel molecular biology patch clamp trafficking channel assembly ion channel Kv1 5 transmembrane domain Shaker superfamily

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RNA Characterization by Solid-State NMR Spectroscopy

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CHEMISTRY-A EUROPEAN JOURNAL 2018年第35期24卷 8698-+页

作者： Yang, Yufei Wang, Shenlin Peking Univ Coll Chem & Mol Engn 5 Yiheyuan Rd Beijing 100871 Peoples R China Peking Univ Beijing NMR Ctr 5 Yiheyuan Rd Beijing 100871 Peoples R China

The structures of RNAs, which play critical roles in various biological processes, provide important clues and insights into the biological functions of these molecules. However, RNA structure determination remains a challenging topic. In recent years, magic-angle-spinning solid-state NMR (MAS SSNMR) has emerged as an alternative technique for structural and dynamic characterization of RNA. MAS SSNMR has been successfully applied to provide atomic-level structural information about several RNA molecules and RNA-protein complexes. In this Minireview, we give an overview of recent progress in the field of MAS SSNMR based RNA structural characterization, and introduce sample preparation strategies and SSNMR spectroscopic techniques that have been incorporated to identify RNA structural elements. We also highlight a few impressive examples of RNAs that have been investigated extensively by SSNMR. Finally, we briefly discuss future technical trends in the use of MAS SSNMR to facilitate RNA structure determination.

关键词： fast magic-angle spinning RNA solid-state NMR spectroscopy structural investigations structure-function relationships

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