bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gain‐of‐function ADCY5 mutations in familial dyskinesia with facial myokymia
Authors: Chen Ying‐Zhang , Friedman Jennifer R. , Chen Dong‐Hui , Chan Guy C.‐K. , Bloss Cinnamon S. , Hisama Fuki M. , Topol Sarah E. , Carson Andrew R. , Pham Phillip H. , Bonkowski Emily S. , Scott Erick R. , Lee Janel K. , Zhang Guangfa , Oliveira Glenn , Xu Jian , Scott‐Van Zeeland Ashley A. , Chen Qi , Levy Samuel , Topol Eric J. , Storm Daniel , Swanson Phillip D. , Bird Thomas D. , Schork Nicholas J. , Raskind Wendy H. , Torkamani Ali 
Published: February 2014

ObjectiveTo identify the cause of childhood onset involuntary paroxysmal choreiform and dystonic movements in 2 unrelated sporadic cases and to investigate the functional effect of missense mutations in adenylyl cyclase 5 (ADCY5) in sporadic and inherited cases of autosomal dominant familial dyskinesia with facial myokymia (FDFM).MethodsWhole exome sequencing was performed on 2 parent–child trios. The effect of mutations in ADCY5 was studied by measurement of cyclic adenosine monophosphate (cAMP) accumulation under stimulatory and inhibitory conditions.ResultsThe same de novo mutation (c.1252C>T, p.R418W) in ADCY5 was found in both studied cases. An inherited missense mutation (c.2176G>A, p.A726T) in ADCY5 was previously reported in a family with FDFM. The significant phenotypic overlap with FDFM was recognized in both cases only after discovery of the molecular link. The inherited mutation in the FDFM family and the recurrent de novo mutation affect residues in different protein domains, the first cytoplasmic domain and the first membrane‐spanning domain, respectively. Functional studies revealed a statistically significant increase in β‐receptor agonist‐stimulated intracellular cAMP consistent with an increase in adenylyl cyclase activity for both mutants relative to wild‐type protein, indicative of a gain‐of‐function effect.InterpretationFDFM is likely caused by gain‐of‐function mutations in different domains of ADCY5—the first definitive link between adenylyl cyclase mutation and human disease. We have illustrated the power of hypothesis‐free exome sequencing in establishing diagnoses in rare disorders with complex and variable phenotype. Mutations in ADCY5 should be considered in patients with undiagnosed complex movement disorders even in the absence of a family history. Ann Neurol 2014;75:542–549
Strukturbasiertes Design von Hemmstoffen der Aspartylprotease Endothiapepsin mittels dynamischer kombinatorischer Chemie
Authors: Mondal Milon , Radeva Nedyalka , Köster Helene , Park Ahyoung , Potamitis Constantinos , Zervou Maria , Klebe Gerhard , Hirsch Anna K. H. 
Published: February 2014

AbstractStrukturbasiertes Design (SBD) wird für den Entwurf und/oder die Optimierung neuer Hemmstoffe für biologische Targets verwendet. Während De‐novo‐SBD selten benutzt wird, befassen sich Berichte über SBD meistens mit der Optimierung eines anfänglichen Hits. Dynamische kombinatorische Chemie (DKC) hat sich bei der die Identifizierung biologisch aktiver Liganden bewährt, da sie es dem Target ermöglicht, die Synthese der stärksten Binder zu steuern. Aus einer Bibliothek möglicher Hemmstoffe (Acylhydrazone), aus je fünf Aldehyden und Hydraziden erzeugt, haben wir mithilfe von DKC den besten Binder identifiziert. Nach Zugabe der Aspartylprotease Endothiapepsin haben wir die an das Protein gebundenen Bibliotheksmitglieder mittels Sättigungstransferdifferenz(STD)‐NMR‐Spektroskopie charakterisiert. Cokristallstrukturen bestätigen den vorhergesagten Bindungsmodus der beiden stärksten Hemmstoffe und zeigen, dass die Kombination von De‐novo‐SBD und DKC eine effiziente Identifizierung und Optimierung von Hits ermöglicht.
Die Isolierung eines labilen homoleptischen Diazeniumkations
Authors: Baumann Wolfgang , Michalik Dirk , Reiß Fabian , Schulz Axel , Villinger Alexander 
Published: February 2014

AbstractUnserem Interesse an der Stickstoffchemie folgend, beschreiben wir hier die Synthese, Struktur und Bindung des labilen disilylierten Diazens, seines GaCl3‐Addukts und des ungewöhnlichen trisilylierten Diazeniumions, [(Me3Si)2NN‐SiMe3]+, ein tiefblaues, äußerst labiles (TZers.>−30 °C) homoleptisches Kation des Typs [R3N2]+. Während die direkte Silylierung des Me3Si‐NN‐SiMe3 scheiterte, konnte das [(Me3Si)2NN‐SiMe3]+‐Ion in einer einfachen Zwei‐Elektronen‐Oxidation ausgehend von Quecksilber(II)‐dihydrazid und Ag[GaCl4] erzeugt werden. Darüber hinaus werden die bisher bekannten Strukturdaten von Me3Si‐NN‐SiMe3 aufgrund neuer Daten korrigiert.
Copper‐Catalyzed Cross‐Coupling of Boronic Esters with Aryl Iodides and Application to the Carboboration of Alkynes and Allenes
Authors: Zhou Yiqing , You Wei , Smith Kevin B. , Brown M. Kevin 
Published: February 2014

AbstractCopper‐catalyzed Suzuki–Miyaura‐type cross‐coupling and carboboration processes are reported. The cross‐couplings function well with a variety of substituted aryl iodides and aryl boronic esters and allows for orthogonal reactivity compared to palladium‐catalyzed processes. The carboboration method includes both alkynes and allenes and provides access to highly substituted and stereodefined vinyl boronic esters. The alkyne carboboration method is highlighted in the simple one‐pot synthesis of Tamoxifen.
Chemically Orthogonal Three‐Patch Microparticles
Authors: Rahmani Sahar , Saha Sampa , Durmaz Hakan , Donini Alessandro , Misra Asish C , Yoon Jaewon , Lahann Joerg 
Published: February 2014

AbstractCompared to two‐dimensional substrates, only a few methodologies exist for the spatially controlled decoration of three‐dimensional objects, such as microparticles. Combining electrohydrodynamic co‐jetting with synthetic polymer chemistry, we were able to create two‐ and three‐patch microparticles displaying chemically orthogonal anchor groups on three distinct surface patches of the same particle. This approach takes advantage of a combination of novel chemically orthogonal polylactide‐based polymers and their processing by electrohydrodynamic co‐jetting to yield unprecedented multifunctional microparticles. Several micropatterned particles were fabricated displaying orthogonal click functionalities. Specifically, we demonstrate novel two‐ and three‐patch particles. Multi‐patch particles are highly sought after for their potential to present multiple distinct ligands in a directional manner. This work clearly establishes a viable route towards orthogonal reaction strategies on multivalent micropatterned particles.
Structure‐Based Design of Inhibitors of the Aspartic Protease Endothiapepsin by Exploiting Dynamic Combinatorial Chemistry
Authors: Mondal Milon , Radeva Nedyalka , Köster Helene , Park Ahyoung , Potamitis Constantinos , Zervou Maria , Klebe Gerhard , Hirsch Anna K. H. 
Published: February 2014

AbstractStructure‐based design (SBD) can be used for the design and/or optimization of new inhibitors for a biological target. Whereas de novo SBD is rarely used, most reports on SBD are dealing with the optimization of an initial hit. Dynamic combinatorial chemistry (DCC) has emerged as a powerful strategy to identify bioactive ligands given that it enables the target to direct the synthesis of its strongest binder. We have designed a library of potential inhibitors (acylhydrazones) generated from five aldehydes and five hydrazides and used DCC to identify the best binder(s). After addition of the aspartic protease endothiapepsin, we characterized the protein‐bound library member(s) by saturation‐transfer difference NMR spectroscopy. Cocrystallization experiments validated the predicted binding mode of the two most potent inhibitors, thus demonstrating that the combination of de novo SBD and DCC constitutes an efficient starting point for hit identification and optimization.
Isolation of a Labile Homoleptic Diazenium Cation
Authors: Baumann Wolfgang , Michalik Dirk , Reiß Fabian , Schulz Axel , Villinger Alexander 
Published: February 2014

AbstractFollowing our interest in nitrogen chemistry, we now describe the synthesis, structure, and bonding of labile disilylated diazene, its GaCl3 adduct, and the intriguing trisilylated diazenium ion [(Me3Si)2NN‐SiMe3]+, a dark blue and highly labile (Tdecomp>−30 °C) homoleptic cation of the type [R3N2]+. Although direct silylation of Me3Si‐NN‐SiMe3 failed, the [(Me3Si)2NN‐SiMe3]+ ion was generated in a straightforward two‐electron oxidation reaction from mercury(II) dihydrazide and Ag[GaCl4]. Moreover, previous structure data of Me3Si‐NN‐SiMe3 were revised on the basis of new data.
Organic multiviologen electrochromic cells for a color electronic display application
Authors: Chen Pin‐Yi , Chen Cheng‐Sao , Yeh Tsung‐Her 
Published: February 2014

ABSTRACTThe electrochromic (EC) and optical properties of three new viologen compounds containing 1,1′‐di‐n‐heptyl‐4,4′‐bipyridinum dibromide (DHBPDB; C24H38Br2N2), 1‐heptyl‐4‐(4‐pyridyl)pyridinium bromide (HPPB; C17H23BrN2), and 1,1′‐dis(p‐cyanophenyl)‐4,4′‐bipyridinium chloride (DCBPC; C12H8N2OBr2) for potential use in electrochromism applications were investigated. The repetitive stability of all of the EC cells could be improved through the addition of ferrocene as an electron donor (a counter redox material) to the electrolyte solution under several redox cycles. The experimental results demonstrate that the EC cell showed a reversible color change from clear (tintless) to three different colors with the application of electrochemical stimuli at specific potentials. The color of the EC cells turned red, green, or blue upon electrochemical reduction for DHBPDB, HPPB, and DCBPC in indium tin oxide sandwich‐type cells. Because of the different viologen molecules competing to capture electrons and affecting the EC efficiency and life of the multiviologen cells, they could be improved by the optimization of the working voltage in the multiviologen cells from the modification of an operative potential based on the cyclic voltammetry measurements. In this article, we propose a prototype device of multicolor electrochromic display, which provides potential application for multicolor electronic displays or EC paper. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40485.
A review of sawfishes (Pristidae) in the Arabian region: diversity, distribution, and functional extinction of large and historically abundant marine vertebrates
Authors: Moore Alec B. M. 
Published: February 2014

Abstract

Sawfishes (Pristidae) are large shark‐like batoids (rays) that are among the most threatened of all marine fishes. While there is a broad consensus of severe sawfish declines globally, detailed status assessments for most of their vast circumtropical distribution do not exist. This paper reviews sawfishes of waters adjacent to the Arabian Peninsula, focusing on the Gulf.
Until around the 1960s, sawfishes were abundant and widespread in the region, but since around the 1980s, they have been rarely recorded. Sawfishes can now be considered extinct as a functional component of coastal ecosystems, and may be close to being regionally extinct. This assessment is based on the overwhelming weight of evidence from diverse sources such as archaeological data, historical accounts, grey literature, personal communications and extensive fish surveys.
Based on 176 individual records, Pristis zijsron was the most frequently recorded species, occurring in all regional seas. Anoxypristis cuspidata records were limited to the coasts of Iran, Pakistan, and Masirah Island (Oman). The first substantiated Pristis pristis records from the Arabian Peninsula are provided, and two records not identifiable to species do not exclude the possibility that Pristis clavata occurs in the region.
Humans have used sawfishes as a food, oil, trade, and cultural resource for several thousands of years. Fins have been highly valued since at least the mid‐19th century.
Based on recent and historical records, known biology, and marine conservation programmes for other species or habitats, priority areas for sawfish research and recovery programmes are the central southern Gulf; significant mangrove areas in Iran and the UAE; the Musandam Peninsula; and Masirah Island (Oman).
Historical regional declines coincide with the widespread availability of nylon gillnets, to which sawfishes are disproportionately vulnerable. Any attempt at sawfish recovery must enforce strict controls on gillnetting, which could have significant benefits for other marine species of commercial and conservation interest.
Copyright © 2014 John Wiley & Sons, Ltd.
Enhanced production of 2,3‐butanediol by overexpressing acetolactate synthase and acetoin reductase in Klebsiella pneumoniae
Authors: Guo Xue‐Wu , Zhang Yun‐Hui , Cao Chun‐Hong , Shen Tong , Wu Ming‐Yue , Chen Ye‐Fu , Zhang Cui‐Ying , Xiao Dong‐Guang 
Published: February 2014

AbstractMutants with overexpression of α‐acetolactate synthase (ALS), α‐acetolactate decarboxylase, and acetoin reductase (AR), either individually or in combination, were constructed to improve 2,3‐butanediol (2,3‐BD) production in Klebsiella pneumoniae. The recombinant strains were characterized in terms of the enzyme activity, 2,3‐BD yield, and expression levels. The recombinant K. pneumoniae strain (KG‐rs) that overexpressed both ALS and AR showed an improved 2,3‐BD yield. When cultured in the media with five different carbon sources (glucose, galactose, fructose, sucrose, and lactose), the mutant exhibited higher 2,3‐BD productivity and production than the parental strain in all the tested carbon sources except for lactose. The 2,3‐BD production of KG‐rs in a batch fermentation with glucose as the carbon source was 12% higher than that of the parental strain.
Fungal secretomes enhance sugar beet pulp hydrolysis
Authors: Kracher Daniel , Oros Damir , Yao Wanying , Preims Marita , Rezic Iva , Haltrich Dietmar , Rezic Tonci , Ludwig Roland 
Published: February 2014

AbstractThe recalcitrance of lignocellulose makes enzymatic hydrolysis of plant biomass for the production of second generation biofuels a major challenge. This work investigates an efficient and economic approach for the enzymatic hydrolysis of sugar beet pulp (SBP), which is a difficult to degrade, hemicellulose‐rich by‐product of the table sugar industry. Three fungal strains were grown on different substrates and the production of various extracellular hydrolytic and oxidative enzymes involved in pectin, hemicellulose, and cellulose breakdown were monitored. In a second step, the ability of the culture supernatants to hydrolyze thermally pretreated SBP was tested in batch experiments. The supernatant of Sclerotium rolfsii, a soil‐borne facultative plant pathogen, was found to have the highest hydrolytic activity on SBP and was selected for further hydrolyzation experiments. A low enzyme load of 0.2 mg g–1 protein from the culture supernatant was sufficient to hydrolyze a large fraction of the pectin and hemicelluloses present in SBP. The addition of Trichoderma reesei cellulase (1–17.5 mg g–1 SBP) resulted in almost complete hydrolyzation of cellulose. It was found that the combination of pectinolytic, hemicellulolytic, and cellulolytic activities works synergistically on the complex SBP composite, and a combination of these hydrolytic enzymes is required to achieve a high degree of enzymatic SBP hydrolysis with a low enzyme load.
Structure of two crystal forms of sheep β‐lactoglobulin with EF‐loop in closed conformation
Authors: Loch Joanna I. , Molenda Marta , Kopeć Magdalena , Świątek Sylwia , Lewiński Krzysztof 
Published: February 2014

ABSTRACTOvine β‐lactoglobulin has been isolated from whey fraction of sheep milk and crystallized. The high‐resolution structures of two crystal forms (triclinic and trigonal) obtained at pH 7.0 have been determined revealing that ovine protein, similarly to its bovine analog, is dimeric. Access to the binding site located in the eight‐stranded antiparallel β‐barrel in both structures is blocked by the EF loop that has been found in closed conformation. Similarly to bovine lactoglobulin (BLG), conformation of the EF loop is stabilized by hydrogen bond between Glu89 and Ser116 indicating that Tanford transition might occur with the same mechanism. The substitution at six positions in relation to the most abundant isoform B of BLG also affects the distribution of electrostatic potentials and the total charge. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 886–894, 2014.
Stabilization of collagen through bioconversion: An insight in protein–protein interaction
Authors: Usharani Nagarajan , Jayakumar Gladstone Christopher , Kanth Swarna Vinodh , Rao Jonnalagadda Raghava 
Published: February 2014

ABSTRACTCollagen is a natural protein, which is used as a vital biomaterial in tissue engineering. The major concern about native collagen is lack of its thermal stability and weak resistance to proteolytic degradation. In this scenario, the crosslinking compounds used for stabilization of collagen are mostly of chemical nature and exhibit toxicity. The enzyme mediated crosslinking of collagen provides a novel alternative, nontoxic method for stabilization. In this study, aldehyde forming enzyme (AFE) is used in the bioconversion of hydroxylmethyl groups of collagen to formyl groups that results in the formation of peptidyl aldehyde. The resulted peptidyl aldehyde interacts with bipolar ions of basic amino acid residues of collagen. Further interaction leads to the formation of conjugated double bonds (aldol condensation involving the aldehyde group of peptidyl aldehyde) within the collagen. The enzyme modified collagen matrices have shown an increase in the denaturation temperature, when compared with native collagen. Enzyme modified collagen membranes exhibit resistance toward collagenolytic activity. Moreover, they exhibited a nontoxic nature. The catalytic activity of AFE on collagen as a substrate establishes an efficient modification, which enhances the structural stability of collagen. This finds new avenues in the context of protein–protein stabilization and discovers paramount application in tissue engineering. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 903–911, 2014.
Systematic review and meta-analysis of cytokeratin 19-based one-step nucleic acid amplification versus histopathology for sentinel lymph node assessment in breast cancer
Authors: Tiernan J P , Verghese E T , Nair A , Pathak S , Kim B , White J , Thygesen H , Horgan K , Hanby A M 
Published: February 2014

Abstract

Background
One-step nucleic acid amplification (OSNA) is a new rapid assay for detecting breast cancer metastases during surgery, saving a second procedure for patients requiring an axillary clearance. Many centres in the UK and abroad have adopted OSNA in place of routine histopathology, despite no published meta-analysis. The aim of this systematic review and meta-analysis was to determine whether intraoperative OSNA for lymph node assessment is comparable to routine histopathology in the detection of clinically relevant metastases.

Methods
PubMed, Embase, Web of Knowledge and regional databases were searched for relevant studies published before December 2012. Included studies compared OSNA and standard histology using fresh lymph nodes that were assessed in a clearly defined systematic manner in accordance with the index study.

Results
Twelve eligible studies were identified that included 5057 lymph nodes from 2192 patients. Although meta-analysis using a random-effects model showed a similar overall proportion of macrometastases detected (429 of 3234 versus 432 of 3234; odds ratio 0·99, 95 per cent confidence interval 0·86 to 1·15), analysis of concordance showed that the pooled positive predictive value for detecting macrometastases was 0·79. This suggests that up to 21 per cent of patients found to have macrometastases using OSNA would have an axillary clearance when histology would have classified the deposits as non-macrometastases. Furthermore, analysis of data from the index publication showed that the range of cytokeratin 19 titres for tumours of a given volume is too wide to predict tumour size.

Conclusion
OSNA has an unacceptably low positive predictive value, leading to axillary clearances that would not be recommended if standard histology had been used to assess the sentinel node.
Arm lymphoedema after axillary surgery in women with invasive breast cancer
Authors: Sackey H , Magnuson A , Sandelin K , Liljegren G , Bergkvist L , Fülep Z , Celebioglu F , Frisell J 
Published: February 2014

Abstract

Background
The primary aim was to compare arm lymphoedema after sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) in women with node-negative and node-positive breast cancer. The secondary aim was to examine the potential association between self-reported and objectively measured arm lymphoedema.

Methods
Women who had surgery during 1999–2004 for invasive breast cancer in four centres in Sweden were included. The study groups were defined by the axillary procedure performed and the presence of axillary metastases: SLNB alone, ALND without axillary metastases, and ALND with axillary metastases. Before surgery, and 1, 2 and 3 years after operation, arm volume was measured and a questionnaire regarding symptoms of arm lymphoedema was completed. A mixed model was used to determine the adjusted mean difference in arm volume between the study groups, and generalized estimating equations were employed to determine differences in self-reported arm lymphoedema.

Results
One hundred and forty women had SLNB alone, 125 had node-negative ALND and 155 node-positive ALND. Women who underwent SLNB had no increase in postoperative arm volume over time, whereas both ALND groups showed a significant increase. The risk of self-reported arm lymphoedema 1, 2 and 3 years after surgery was significantly lower in the SLNB group compared with that in both ALND groups. Three years after surgery there was a significant association between increased arm volume and self-reported symptoms of arm lymphoedema.

Conclusion
SLNB is associated with a minimal risk of increased arm volume and few symptoms of arm lymphoedema, significantly less than after ALND, regardless of lymph node status.
Biochemistry students' ideas about shape and charge in enzyme–substrate interactions
Authors: Linenberger Kimberly J. , Bretz Stacey Lowery 
Published: February 2014

AbstractBiochemistry is a visual discipline that requires students to develop an understanding of numerous representations. However, there is very little known about what students actually understand about the representations that are used to communicate ideas in biochemistry. This study investigated biochemistry students' understanding of multiple representations of enzyme–substrate interactions through both student interviews (N = 25) and responses by a national sample (N = 707) to the Enzyme–Substrate Interactions Concept Inventory. This manuscript reports the findings regarding one category of misconceptions measured by the concept inventory, namely, students' understandings of shape and charge in the context of enzyme–substrate interactions. Students interpret molecular representations depicting such interactions by determining the complementarity between enzyme and substrate by focusing upon charge and hydrogen bonding, but with a disregard for stereochemistry. © 2014 by The International Union of Biochemistry and Molecular Biology, 42(3):XXXXX–XXXXX, 2014.