bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Mexico to Michigan and back: An international collaboration investigating primate behavior, ecology, and evolution from multiple perspectives
Authors: Cortés‐Ortiz Liliana , Espinosa Domingo Canales , Dias Pedro D. , Bergman Thore , Kitchen Dawn M. 
Published: June 2019

AbstractEvolutionary research benefits form the integration of laboratory and field components to determine factors and processes that affect the evolutionary trajectories of species. Our shared interest in understanding hybridization with genetic admixture as a process that may impact social, behavioral, and ecological features of primates, brought us together in a collaborative project aimed at addressing how vocal variation in two species of howler monkeys in Mexico affects and is affected by hybridization. To achieve this goal, we joined our academic expertise in studying primate genetics, ecology, and behavior under different natural and experimental conditions. We took advantage of decades of experience studying and handing wild howler monkeys for translocation projects to safely sample and study wild populations for this project. Here, we describe the history of our collaboration highlighting how our different perspectives, academic realities, and individual strengths built the foundation for our successful collaboration. We also share our perspectives on how this collaboration opened up new academic venues, broadened our individual perspectives on the integration of different research approaches to address a complex topic, and allowed us to recognize the strength of international collaboration.
Presymptomatic spinal cord pathology in c9orf72 mutation carriers: A longitudinal neuroimaging study
Authors: Querin Giorgia , Bede Peter , El Mendili Mohamed Mounir , Li Menghan , Pélégrini‐Issac Mélanie , Rinaldi Daisy , Catala Martin , Saracino Dario , Salachas François , Camuzat Agnes , Marchand‐Pauvert Véronique , Cohen‐Adad Julien , Colliot Olivier , Le Ber Isabelle , Pradat Pierre‐François ,   for the Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Study Group
Published: June 2019

ObjectiveC9orf72 hexanucleotide repeats expansions account for almost half of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases. Recent imaging studies in asymptomatic C9orf72 carriers have demonstrated cerebral white (WM) and gray matter (GM) degeneration before the age of 40 years. The objective of this study was to characterize cervical spinal cord (SC) changes in asymptomatic C9orf72 hexanucleotide carriers.MethodsSeventy‐two asymptomatic individuals were enrolled in a prospective study of first‐degree relatives of ALS and FTD patients carrying the c9orf72 hexanucleotide expansion. Forty of them carried the pathogenic mutation (C9+). Each subject underwent quantitative cervical cord imaging. Structural GM and WM metrics and diffusivity parameters were evaluated at baseline and 18 months later. Data were analyzed in C9+ and C9− subgroups, and C9+ subjects were further stratified by age.ResultsAt baseline, significant WM atrophy was detected at each cervical vertebral level in C9+ subjects older than 40 years without associated changes in GM and diffusion tensor imaging parameters. At 18‐month follow‐up, WM atrophy was accompanied by significant corticospinal tract (CST) fractional anisotropy (FA) reductions. Intriguingly, asymptomatic C9+ subjects older than 40 years with family history of ALS (as opposed to FTD) also exhibited significant CST FA reduction at baseline.InterpretationCervical SC imaging detects WM atrophy exclusively in C9+ subjects older than 40 years, and progressive CST FA reductions can be identified on 18‐month follow‐up. Cervical SC magnetic resonance imaging readily captures presymptomatic pathological changes and disease propagation in c9orf72‐associated conditions. ANN NEUROL 2019;86:158–167
A functional substitution in the L‐aromatic amino acid decarboxylase enzyme worsens somatic symptoms via a serotonergic pathway
Authors: Khoury Samar , Piltonen Marjo H. , Ton Anh‐Tien , Cole Tiffany , Samoshkin Alexander , Smith Shad B. , Belfer Inna , Slade Gary D. , Fillingim Roger B. , Greenspan Joel D. , Ohrbach Richard , Maixner William , Neely G. Gregory , Serohijos Adrian W. R. , Diatchenko Luda 
Published: June 2019

ObjectiveHeightened somatic symptoms are reported by a wide range of patients with chronic pain and have been associated with emotional distress and physical dysfunction. Despite their clinical significance, molecular mechanisms leading to their manifestation are not understood.MethodsWe used an association study design based on a curated list of 3,295 single nucleotide polymorphisms mapped to 358 genes to test somatic symptoms reporting using the Pennebaker Inventory of Limbic Languidness questionnaire from a case–control cohort of orofacial pain (n = 1,607). A replication meta‐analysis of 3 independent cohorts (n = 3,189) was followed by functional validation, including in silico molecular dynamics, in vitro enzyme assays, and measures of serotonin (5‐HT) plasma concentration.ResultsAn association with the T allele of rs11575542 coding for an arginine to glutamine substitution in the L‐aromatic amino acid decarboxylase (AADC) enzyme was replicated in a meta‐analysis of 3 independent cohorts. In a combined meta‐analysis of all cohorts, this association reached p = 6.43 × 10−8. In silico studies demonstrated that this substitution dramatically reduces the conformational dynamics of AADC, potentially lowering its binding capacity to a cofactor. in vitro enzymatic assays showed that this substitution reduces the maximum kinetic velocity of AADC, hence lowering 5‐HT levels. Finally, plasma samples from 90 subjects showed correlation between low 5‐HT levels and heightened somatic symptoms.InterpretationUsing functional genomics approaches, we identified a polymorphism in the AADC enzyme that contributes to somatic symptoms through reduced levels of 5‐HT. Our findings suggest a molecular mechanism underlying the pathophysiology of somatic symptoms and opens up new treatment options targeting the serotonergic system. ANN NEUROL 2019;86:168–180
Autism and developmental disability caused by KCNQ3 gain‐of‐function variants
Authors: Sands Tristan T. , Miceli Francesco , Lesca Gaetan , Beck Anita E. , Sadleir Lynette G. , Arrington Daniel K. , Schönewolf‐Greulich Bitten , Moutton Sébastien , Lauritano Anna , Nappi Piera , Soldovieri Maria Virginia , Scheffer Ingrid E. , Mefford Heather C. , Stong Nicholas , Heinzen Erin L. , Goldstein David B. , Perez Ana Grijalvo , Kossoff Eric H. , Stocco Amber , Sullivan Jennifer A. , Shashi Vandana , Gerard Benedicte , Francannet Christine , Bisgaard Anne‐Marie , Tümer Zeynep , Willems Marjolaine , Rivier François , Vitobello Antonio , Thakkar Kavita , Rajan Deepa S. , Barkovich A. James , Weckhuysen Sarah , Cooper Edward C. , Taglialatela Maurizio , Cilio M. Roberta 
Published: June 2019

ObjectiveRecent reports have described single individuals with neurodevelopmental disability (NDD) harboring heterozygous KCNQ3 de novo variants (DNVs). We sought to assess whether pathogenic variants in KCNQ3 cause NDD and to elucidate the associated phenotype and molecular mechanisms.MethodsPatients with NDD and KCNQ3 DNVs were identified through an international collaboration. Phenotypes were characterized by clinical assessment, review of charts, electroencephalographic (EEG) recordings, and parental interview. Functional consequences of variants were analyzed in vitro by patch‐clamp recording.ResultsEleven patients were assessed. They had recurrent heterozygous DNVs in KCNQ3 affecting residues R230 (R230C, R230H, R230S) and R227 (R227Q). All patients exhibited global developmental delay within the first 2 years of life. Most (8/11, 73%) were nonverbal or had a few words only. All patients had autistic features, and autism spectrum disorder (ASD) was diagnosed in 5 of 11 (45%). EEGs performed before 10 years of age revealed frequent sleep‐activated multifocal epileptiform discharges in 8 of 11 (73%). For 6 of 9 (67%) recorded between 1.5 and 6 years of age, spikes became near‐continuous during sleep. Interestingly, most patients (9/11, 82%) did not have seizures, and no patient had seizures in the neonatal period. Voltage‐clamp recordings of the mutant KCNQ3 channels revealed gain‐of‐function (GoF) effects.InterpretationSpecific GoF variants in KCNQ3 cause NDD, ASD, and abundant sleep‐activated spikes. This new phenotype contrasts both with self‐limited neonatal epilepsy due to KCNQ3 partial loss of function, and with the neonatal or infantile onset epileptic encephalopathies due to KCNQ2 GoF. ANN NEUROL 2019;86:181–192
Utilizing Carbonyl Coordination of Native Amides for Palladium‐Catalyzed C(sp3)−H Olefination
Authors: Park Hojoon , Li Yang , Yu Jin‐Quan 
Published: June 2019

AbstractPdII‐catalyzed C(sp3)−H olefination of weakly coordinating native amides is reported. Three major drawbacks of previous C(sp3)−H olefination protocols, 1) in situ cyclization of products, 2) incompatibility with α‐H‐containing substrates, and 3) installation of exogenous directing groups, are addressed by harnessing the carbonyl coordination ability of amides to direct C(sp3)−H activation. The method enables direct C(sp3)−H functionalization of a wide range of native amide substrates, including secondary, tertiary, and cyclic amides, for the first time. The utility of this process is demonstrated by diverse transformations of the olefination products.
The Double‐Faced Nature of Hydrogen Bonding in Hydroxy‐Functionalized Ionic Liquids Shown by Neutron Diffraction and Molecular Dynamics Simulations
Authors: Niemann Thomas , Neumann Jan , Stange Peter , Gärtner Sabrina , Youngs Tristan G. A. , Paschek Dietmar , Warr Gregory G. , Atkin Rob , Ludwig Ralf 
Published: June 2019

AbstractWe characterize the double‐faced nature of hydrogen bonding in hydroxy‐functionalized ionic liquids by means of neutron diffraction with isotopic substitution (NDIS), molecular dynamics (MD) simulations, and quantum chemical calculations. NDIS data are fit using the empirical potential structure refinement technique (EPSR) to elucidate the nearest neighbor H⋅⋅⋅O and O⋅⋅⋅O pair distribution functions for hydrogen bonds between ions of opposite charge and the same charge. Despite the presence of repulsive Coulomb forces, the cation–cation interaction is stronger than the cation–anion interaction. We compare the hydrogen‐bond geometries of both “doubly charged hydrogen bonds” with those reported for molecular liquids, such as water and alcohols. In combination, the NDIS measurements and MD simulations reveal the subtle balance between the two types of hydrogen bonds: The small transition enthalpy suggests that the elusive like‐charge attraction is almost competitive with conventional ion‐pair formation.
Hyperaging Tuning of a Carbon Molecular‐Sieve Hollow Fiber Membrane with Extraordinary Gas‐Separation Performance and Stability
Authors: Qiu Wulin , Vaughn Justin , Liu Gongping , Xu Liren , Brayden Mark , Martinez Marcos , Fitzgibbons Thomas , Wenz Graham , Koros William J. 
Published: June 2019

AbstractThis study reports 6FDA:BPDA‐DAM polyimide‐derived hollow fiber carbon molecular‐sieve (CMS) membranes for hydrogen and ethylene separation. Since H2/C2H4 selectivity is the lowest among H2/(C1‐C3) hydrocarbons, an optimized CMS fiber for this gas pair is useful for removing hydrogen from all‐cracked gas mixtures. A process we term hyperaging provides highly selective CMS fiber membranes by tuning CMS ultramicropores to favor H2 over larger molecules to give a H2/C2H4 selectivity of over 250. Hyperaging conditions and a hyperaging mechanism are discussed in terms of an expedited physical aging process, which is largely controlled by the hyperaging temperature. For the specific CMS material considered here, a hyperaging temperature beyond 90 °C but less than 250 °C works best. Hyperaging also stabilizes CMS materials against physical aging and stabilizes the performance of H2 separation over extended periods. This work opens a door in the development of CMS materials for the separation of small molecules from large molecules.
Near‐Infrared‐Light‐Triggered Antimicrobial Indium Phosphide Quantum Dots
Authors: Levy Max , Bertram John R. , Eller Kristen A. , Chatterjee Anushree , Nagpal Prashant 
Published: June 2019

AbstractThe emergence of multidrug‐resistant (MDR) pathogens represents one of the most urgent global public health crises. Light‐activated quantum dots (QDs) are alternative antimicrobials, with efficient transport, low cost, and therapeutic efficacy, and they can act as antibiotic potentiators, with a mechanism of action orthogonal to small‐molecule drugs. Furthermore, light‐activation enhances control over the spatiotemporal release and dose of the therapeutic superoxide radicals from QDs. However, the limited deep‐tissue penetration of visible light needed for QD activation, and concern over trace heavy metals, have prevented further translation. Herein, we report two indium phosphide (InP) QDs that operate in the near‐infrared and deep‐red light window, enabling deeper tissue penetration. These heavy‐metal‐free QDs eliminate MDR pathogenic bacteria, while remaining non‐toxic to host human cells. This work provides a pathway for advancing QD nanotherapeutics to combat MDR superbugs.
Modulating Guest Uptake in Core–Shell MOFs with Visible Light
Authors: Mutruc Dragos , Goulet‐Hanssens Alexis , Fairman Sam , Wahl Sebastian , Zimathies Annett , Knie Christopher , Hecht Stefan 
Published: June 2019

AbstractA two‐component core–shell UiO‐68 type metal–organic framework (MOF) with a nonfunctionalized interior for efficient guest uptake and storage and a thin light‐responsive outer shell was prepared by initial solvothermal MOF synthesis followed by solvent‐assisted linker exchange. The bulky shell linker features two tetra‐ortho‐fluorinated azobenzene moieties to exploit their advantageous photoisomerization properties. The obtained perfect octahedral MOF single crystals can be switched repeatedly and with an unprecedented efficiency between E‐ and Z‐rich states using visible light only. Due to the high photoswitch density per pore of the shell layer, its steric demand and thus molecular uptake (and release) can be conveniently modulated upon green and blue light irradiation. Therefore, the “smart” shell acts as a light‐controlled kinetic barrier or “gate” for the diffusion of cargo molecules in and out of the MOF crystals.
RETRACTED: Bufothionine Promotes Apoptosis via Triggering ER Stress and Synergizes with Temozolomide in Glioblastoma Multiforme Cells
Authors: Sun Yafeng , Zhang Xianhong 
Published: June 2019

ABSTRACTGlioblastoma multiforme (GBM) is the most common type of malignant glioma. Bufothionine is one of the major active ingredients of Cinobufacini. Although the antitumor activities of bufothionine have been reported, the underlying mechanism remains unclear. The present study showed that bufothionine exhibited antigrowth activities in GBM cell lines U87 and U373. Further investigation showed that bufothionine triggered endoplasmic reticulum (ER) stress to promote apoptosis in U87 and U373 cells. Moreover, our results showed that bufothionine exhibited synergistic activities with Temozolomide (TMZ) to suppress the growth of U87 and U373 cells. The findings in the present study provide basis for further investigation of the therapeutic potential of bufothionine in GBM. Anat Rec, 302:1950–1957, 2019. © 2019 American Association for Anatomy
A Quantitative and Comparative Analysis of the Muscle Architecture of the Forelimb Myology of Diurnal Birds of Prey (Order Accipitriformes and Falconiformes)
Authors: Bribiesca‐Contreras Fernanda , Parslew Ben , Sellers William I. 
Published: June 2019

ABSTRACTFlight is a key feature in the evolution of birds. Wing anatomy reflects many aspects of avian biology such as flight ability. However, our knowledge of the flight musculature has many gaps still, particularly for the distal wing. Therefore, the aim of this work was to investigate the form–function relationship of the forelimb myology of birds to understand the role of individual muscles during flight. Dissections of six species of birds of prey were performed to collect numerical data of muscle architecture, which is the primary determinant of muscle function and force‐generation capacity. Birds of prey are a highly diverse group that presents different flight styles throughout the taxa, making them a good model for our purposes. Wing muscle mass (MM) isometrically scaled with body mass1.035, muscle length to MM0.343, and fascicle length (FL) scaled allometrically to MM0.285. The shoulder musculature scaled differently than the other regions where the FL increases more slowly than would be expected in geometrically similar animals, which affects flight mechanics. A proximal‐to‐distal reduction of MM occurs, which helps to minimize the wing moment of inertia during flight while allowing precise control of the distal wing. Interestingly, the distribution of MM appeared to be species‐specific, suggesting a functional signal. This study provides numerical information of muscle architecture of the avian wing that helps us to understand muscle function and its implication in flight, and can be used in future studies of flight mechanics. Anat Rec, 302:1808–1823, 2019. © 2019 American Association for Anatomy
Long‐Term Fine Motor Capability on the Staircase Test Correlates with the Absolute Number, but Not the Density, of DARPP‐Positive Neurons in the Caudate‐Putamen
Authors: Aghoghovwia Benjamin E. , Goddard Liping , Oorschot Dorothy E. 
Published: June 2019

ABSTRACTMeasurement of long‐term functional and anatomical outcomes in the same animal is considered a powerful strategy for correlating structure with function. In a neonatal animal model of hypoxic–ischemic brain injury that is relevant to cerebral palsy, long‐term functional deficits on the staircase test and long‐term anatomical deficits in the absolute number of medium‐spiny projection neurons in the caudate‐putamen were reported in different animals due to logistical constraints. Here, we investigated if these functional and anatomical measures were correlated when measured in the same animals. The medium‐spiny projection neurons were investigated because (1) they comprise the vast majority (>97%) of all neurons in the caudate‐putamen and (2) motor deficits observed during staircase testing are likely to involve these striatal medium‐spiny projection neurons through their connections. We found that long‐term skilled forepaw capability on the staircase test was correlated with the absolute number of DARPP‐32‐positive medium‐spiny projection neurons in the caudate‐putamen. Specifically, deficits in skilled forepaw ability for the number of sugar pellets eaten and retrieved, and for the maximum staircase level reached, were significantly correlated with a lower absolute neuronal number. We also found that skilled forepaw ability on the staircase test was not correlated with the neuronal density (i.e., number per unit volume) of DARPP‐32‐positive medium‐spiny projection neurons. Since neuronal density is an indirect measure of neuronal survival that is used in the literature, and absolute neuronal number is a direct measure, the results also highlight the scientific value of measuring absolute neuronal number. Anat Rec, 302:2040–2048, 2019. © 2019 American Association for Anatomy
The Cephalic Osteoderms of Varanus komodoensis as Revealed by High‐Resolution X‐Ray Computed Tomography
Authors: Maisano Jessica A. , Laduc Travis J. , Bell Christopher J. , Barber Diane 
Published: June 2019

ABSTRACTOsteoderms constitute a morphological system that plays an important role in squamate systematics. However, their study and visualization have always been difficult due to their isolated occurrence in the skin, among the first organs to be removed during the skeletonization process. High‐resolution X‐ray computed tomography (HRXCT) offers a nondestructive means of visualizing osteoderms both in their natural relationship to each other and to the underlying cranial bones. Although it is often stated that Varanus komodoensis has a “chain mail” of osteoderms, this morphological system was never described in this taxon. Further, given its size, it might be expected that V. komodoensis would present the extreme of osteoderm development in extant varanids, a group that tends to have weakly developed osteoderms or none at all. Indeed, our HRXCT scan of a 19‐year‐old captive individual reveals an elaborate mesh of cephalic osteoderms that are incredibly numerous and morphologically diverse. We describe this skeletal system and compare it to the cephalic osteoderms in other varanoids. Anat Rec, 302:1675–1680, 2019. © 2019 American Association for Anatomy
Metabolomic profiling of CHO fed‐batch growth phases at 10, 100, and 1,000 L
Authors: Vodopivec Maja , Lah Ljerka , Narat Mojca , Curk Tomaž 
Published: June 2019

AbstractEstablished bioprocess monitoring is based on quick and reliable methods, including cell count and viability measurement, extracellular metabolite measurement, and the measurement of physicochemical qualities of the cultivation medium. These methods are sufficient for monitoring of process performance, but rarely give insight into the actual physiological states of the cell culture. However, understanding of the latter is essential for optimization of bioprocess development. Our study used LC‐MS metabolomics as a tool for additional resolution of bioprocess monitoring and was designed at three bioreactors scales (10 L, 100 L, and 1,000 L) to gain insight into the basal metabolic states of the Chinese hamster ovary (CHO) cell culture during fed‐batch. Metabolites characteristics of the four growth stages (early and late exponential phase, stationary phase, and the phase of decline) were identified by multivariate analysis. Enriched metabolic pathways were then established for each growth phase using the CHO metabolic network model. Biomass generation and nucleotide synthesis were enriched in early exponential phase, followed by increased protein production and imbalanced glutathione metabolism in late exponential phase. Glycolysis became downregulated in stationary phase and amino‐acid metabolism increased. Phase of culture decline resulted in rise of oxidized glutathione and fatty acid concentrations. Intracellular metabolic profiles of the CHO fed‐batch culture were also shown to be consistent with scale and thus demonstrate metabolomic profiling as an informative method to gain physiological insight into the cell culture states during bioprocess regardless of scale.