bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation
Authors: Klontz Erik H. , Li Chao , Kihn Kyle , Fields James K. , Beckett Dorothy , Snyder Greg A. , Wintrode Patrick L. , Deredge Daniel , Wang Lai-Xi , Sundberg Eric J. 
Published: December 2020

AbstractFucosylation is important for the function of many proteins with biotechnical and medical applications. Alpha-fucosidases comprise a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins.Lactobacillus caseiproduces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in humanN-glycan core fucosylation. AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibodyN-glycans, with significant impacts on their effector functions. Despite the potential uses for AlfC, little is known about its mechanism. Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen–deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants. Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
Heat Shock Factor 1-dependent extracellular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancer
Authors: Levi-Galibov Oshrat , Lavon Hagar , Wassermann-Dozorets Rina , Pevsner-Fischer Meirav , Mayer Shimrit , Wershof Esther , Stein Yaniv , Brown Lauren E. , Zhang Wenhan , Friedman Gil , Nevo Reinat , Golani Ofra , Katz Lior H. , Yaeger Rona , Laish Ido , Porco John A. , Sahai Erik , Shouval Dror S. , Kelsen David , Scherz-Shouval Ruth 
Published: December 2020

AbstractIn the colon, long-term exposure to chronic inflammation drives colitis-associated colon cancer (CAC) in patients with inflammatory bowel disease. While the causal and clinical links are well established, molecular understanding of how chronic inflammation leads to the development of colon cancer is lacking. Here we deconstruct the evolving microenvironment of CAC by measuring proteomic changes and extracellular matrix (ECM) organization over time in a mouse model of CAC. We detect early changes in ECM structure and composition, and report a crucial role for the transcriptional regulator heat shock factor 1 (HSF1) in orchestrating these events. Loss of HSF1 abrogates ECM assembly by colon fibroblasts in cell-culture, prevents inflammation-induced ECM remodeling in mice and inhibits progression to CAC. Establishing relevance to human disease, we find high activation of stromal HSF1 in CAC patients, and detect the HSF1-dependent proteomic ECM signature in human colorectal cancer. Thus, HSF1-dependent ECM remodeling plays a crucial role in mediating inflammation-driven colon cancer.
Benzene- and pyridine-incorporated octaphyrins with different coordination modes toward two PdII centers
Authors: Liu Le , Hu Zhiwen , Zhang Fenni , Liu Yang , Xu Ling , Zhou Mingbo , Tanaka Takayuki , Osuka Atsuhiro , Song Jianxin 
Published: December 2020

AbstractExpanded porphyrins have received considerable attention due to their unique optical, electrochemical and coordination properties. Here, we report benzene- and pyridine-incorporated octaphyrins(1.1.0.0.1.1.0.0), which are synthesized through Suzuki-Miyaura coupling of α,α′-diboryltripyrrane with m-dibromobenzene and 2,6-dibromopyridine, respectively, and subsequent oxidation with 2,3-dicyano-5,6-dichlorobenzoquinone. Both octaphyrins are nonaromatic and take on dumbbell structures. Upon treatment with Pd(OOCCH3)2, the benzene-incorporated one gives a Ci symmetric NNNC coordinated bis-PdII complex but the pyridine incorporated one gives Ci and Cs symmetric NNNC coordinated bis-PdII complexes along with an NNNN coordinated bis-PdII complex bearing a transannular C–C bond between the pyrrole α-positions. In addition, these two pyridine-containing NNNC PdII complexes undergo trifluoroacetic acid-induced clean interconversion.
Small molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells
Authors: Tremblay Cedric S. , Chiu Sung Kai , Saw Jesslyn , McCalmont Hannah , Litalien Veronique , Boyle Jacqueline , Sonderegger Stefan E. , Chau Ngoc , Evans Kathryn , Cerruti Loretta , Salmon Jessica M. , McCluskey Adam , Lock Richard B. , Robinson Phillip J. , Jane Stephen M. , Curtis David J. 
Published: December 2020

AbstractIntensive chemotherapy for acute leukemia can usually induce complete remission, but fails in many patients to eradicate the leukemia stem cells responsible for relapse. There is accumulating evidence that these relapse-inducing cells are maintained and protected by signals provided by the microenvironment. Thus, inhibition of niche signals is a proposed strategy to target leukemia stem cells but this requires knowledge of the critical signals and may be subject to compensatory mechanisms. Signals from the niche require receptor-mediated endocytosis, a generic process dependent on the Dynamin family of large GTPases. Here, we show that Dynole 34-2, a potent inhibitor of Dynamin GTPase activity, can block transduction of key signalling pathways and overcome chemoresistance of leukemia stem cells. Our results provide a significant conceptual advance in therapeutic strategies for acute leukemia that may be applicable to other malignancies in which signals from the niche are involved in disease progression and chemoresistance.
Morphological evolution of Pt-modified nanoporous gold after thermal coarsening in reductive and oxidative environments
Authors: El-Zoka A. A. , Langelier B. , Botton G. A. , Newman R. C. 
Published: December 2020

AbstractNanoporous gold made by dealloying AgAuPt (NPG-Pt) has been shown to exhibit several interesting catalytic properties, tied to its exceptionally high surface area; however, structural degradation may occur owing to thermal coarsening. To understand the effect of atmosphere chemistry on thermal coarsening and degradation, and means of limiting it, this study focuses on the high-resolution characterization of NPG-Pt layers coarsened in reductive Ar-H2 atmosphere, and in oxidative air. Atom probe tomography (APT) analysis is performed on NPG-Pt, coarsened separately in either Ar-H2 or air, to characterize the atomic-scale chemical changes in the nanoligaments and to develop a mechanistic view of the inherent processes. A tendency of Ag to segregate to the surface during coarsening is found to lead to complete elimination of the nanoligament core-shell structures in both cases. Large Pt segregates form during coarsening in Ar-H2, but under the surface of the ligaments, having relatively little effect on the coarsening rate. The oxygen-induced segregation of Pt was observed to cause the inhibition of thermal coarsening after minor loss in surface area-to-volume ratio. Findings in this paper help in understanding further the thermal coarsening of heterogeneous nanomaterials made by dealloying, and the pertinent factors that come into play in different chemical environments.
Cerebrospinal fluid glutamate changes in functional movement disorders
Authors: Demartini Benedetta , Invernizzi Roberto William , Campiglio Laura , Bocci Tommaso , D’Arrigo Andrea , Arighi Andrea , Sciacca Francesca , Galimberti Daniela , Scarpini Elio , Gambini Orsola , Priori Alberto 
Published: December 2020

AbstractThe aim of this study was to assess cerebrospinal fluid (CSF) concentrations of specific amino acids using a high-performance liquid chromatography system in a sample of patients with functional movement disorders (FMDs) and in a sample of controls. CSF levels of glutamate were significantly lower in patients with FMD than in controls. This finding argues in favor of glutamatergic dysfunction in the pathophysiology of FMD.
Verification of a resetting protocol for an uncontrolled superconducting qubit
Authors: Gong Ming , Xu Feihu , Li Zheng-Da , Wang Zizhu , Zhang Yu-Zhe , Wu Yulin , Li Shaowei , Zhao Youwei , Wang Shiyu , Zha Chen , Deng Hui , Yan Zhiguang , Rong Hao , Liang Futian , Lin Jin , Xu Yu , Guo Cheng , Sun Lihua , Clark Juno , Peng Cheng-Zhi , Chen Yu-Ao , Zhu Xiaobo , Pan Jian-Wei 
Published: December 2020

Abstract
Quantum resetting protocols allow a quantum system to be sent to a state in the past by making it interact with quantum probes when neither the free evolution of the system nor the interaction is controlled. We experimentally verify the simplest non-trivial case of a quantum resetting protocol, known as the

$${{\mathcal{W}}}_{4}$$

W

4

protocol, with five superconducting qubits, testing it with different types of free evolutions and target–probe interactions. After projection, we obtained a reset state fidelity as high as 0.951, and the process fidelity was found to be 0.792. We also implemented 100 randomly chosen interactions and demonstrated an average success probability of 0.323 for

$$\left|1\right\rangle$$

1

and 0.292 for

$$\left|-\right\rangle$$

−

, and experimentally confirmed the nonzero probability of success for unknown interactions; the numerical simulated values are about 0.3. Our experiment shows that the simplest quantum resetting protocol can be implemented with current technologies, making such protocols a valuable tool in the eternal fight against unwanted evolution in quantum systems.
MnBi2Te4-family intrinsic magnetic topological materials
Authors: He Ke 
Published: December 2020

AbstractMnBi2Te4 and its derivative compounds have received focused research interests recently for their inherent magnetic order and the rich, robust and tunable topological phases hosted in them. Here, I briefly introduce MnBi2Te4-family intrinsic magnetic topological materials—the electronic and magnetic properties, the topological phase diagrams and the research progress made on them in the past years. I try to present a simple picture to understand their rich electronic, magnetic and topological properties, and a concise guide to engineer them for intended topological phases and the quantum anomalous Hall effect at higher temperature.
ClimateEU, scale-free climate normals, historical time series, and future projections for Europe
Authors: Marchi Maurizio , Castellanos-Acuña Dante , Hamann Andreas , Wang Tongli , Ray Duncan , Menzel Annette 
Published: December 2020

AbstractInterpolated climate data have become essential for regional or local climate change impact assessments and the development of climate change adaptation strategies. Here, we contribute an accessible, comprehensive database of interpolated climate data for Europe that includes monthly, annual, decadal, and 30-year normal climate data for the last 119 years (1901 to 2019) as well as multi-model CMIP5 climate change projections for the 21st century. The database also includes variables relevant for ecological research and infrastructure planning, comprising more than 20,000 climate grids that can be queried with a provided ClimateEU software package. In addition, 1 km and 2.5 km resolution gridded data generated by the software are available for download. The quality of ClimateEU estimates was evaluated against weather station data for a representative subset of climate variables. Dynamic environmental lapse rate algorithms employed by the software to generate scale-free climate variables for specific locations lead to improvements of 10 to 50% in accuracy compared to gridded data. We conclude with a discussion of applications and limitations of this database.
Altered regional homogeneity and functional brain networks in Type 2 diabetes with and without mild cognitive impairment
Authors: Xiong Ying , Chen Xiaodan , Zhao Xu , Fan Yang , Zhang Qiang , Zhu Wenzhen 
Published: December 2020

AbstractPatients with Type-2 Diabetes Mellitus (T2DM) have a considerably higher risk of developing mild cognitive impairment (MCI) and dementia. The initial symptoms are very insidious at onset. We investigated the alterations in spontaneous brain activity and network connectivity through regional homogeneity (ReHo) and graph theoretical network analyses, respectively, of resting-state functional Magnetic Resonance Imaging (rs-fMRI) in T2DM patients with and without MCI, so as to facilitate early diagnose. Twenty-five T2DM patients with MCI (DM-MCI), 25 T2DM patients with normal cognition (DM-NC), 27 healthy controls were enrolled. Whole-brain ReHo values were calculated and topological properties of functional networks were analyzed. The DM-MCI group exhibited decreased ReHo in the left inferior/middle occipital gyrus and right inferior temporal gyrus, and increased ReHo in frontal gyrus compared to the DM-NCs. Significant correlations were found between ReHo values and clinical measurements. The DM-MCI group illustrated greater clustering coefficient/local efficiency and altered nodal characteristics (efficiency, degree and betweenness), which increased in certain occipital, temporal and parietal regions but decreased in the right inferior temporal gyrus, compared to the DM-NCs. The altered ReHo and impaired network organization may underlie the impaired cognitive functions in T2DM and suggesting a compensation mechanism. These rs-fMRI measures have the potential as biomarkers of disease progression in diabetic encephalopathy.
Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium
Authors: Amit Chatterjee , Padmanabhan Prema , Narayanan Janakiraman 
Published: December 2020

AbstractKeratoconus (KC) is a corneal dystrophy characterized by progressive ectasia that leads to severe visual impairment and remains one of the leading indications for corneal transplantation. The etiology is believed to be multifactorial and alterations have been documented in the biomechanical, biochemical and ultrastructural characteristics of the cornea. While the exact site of disease origin is still debated, changes in the corneal epithelium are believed to occur even before the disease is clinically manifested. In this study we investigate the possible role of β-catenin as mechanotransducer in KC corneal epithelium. The sheets of corneal epithelium removed from keratoconic eyes when they underwent collagen crosslinking as a therapeutic procedure were used for this study. The healthy corneal epithelium of patients undergoing Laser Refractive Surgery for the correction of their refractive error, served as controls. Immunoblotting and tissue immunofluorescence studies were performed on KC epithelium to analyse the expression and localization of β-catenin, E-cadherin, ZO1, α-catenin, Cyclin D1, α-actinin, RhoA, and Rac123. Co-immunoprecipitation of β-catenin followed by mass spectrometry of KC epithelium was performed to identify its interacting partners. This was further validated by using epithelial tissues grown on scaffolds of different stiffness. Histology data reported breaks in the Bowman’s layer in KC patients. We hypothesize that these breaks expose the epithelium to the keratoconic corneal stroma, which, is known to have a decreased elastic modulus and that β-catenin acts as a mechanotransducer that induces structural changes such as loss of polarity (Syntaxin3) and barrier function (ZO1) through membrane delocalization. The results of our study strongly suggest that β-catenin could be a putative mechanotransducer in KC epithelium, thus supporting our hypothesis.
Multiscale classification of heart failure phenotypes by unsupervised clustering of unstructured electronic medical record data
Authors: Nagamine Tasha , Gillette Brian , Pakhomov Alexey , Kahoun John , Mayer Hannah , Burghaus Rolf , Lippert Jörg , Saxena Mayur 
Published: December 2020

AbstractAs a leading cause of death and morbidity, heart failure (HF) is responsible for a large portion of healthcare and disability costs worldwide. Current approaches to define specific HF subpopulations may fail to account for the diversity of etiologies, comorbidities, and factors driving disease progression, and therefore have limited value for clinical decision making and development of novel therapies. Here we present a novel and data-driven approach to understand and characterize the real-world manifestation of HF by clustering disease and symptom-related clinical concepts (complaints) captured from unstructured electronic health record clinical notes. We used natural language processing to construct vectorized representations of patient complaints followed by clustering to group HF patients by similarity of complaint vectors. We then identified complaints that were significantly enriched within each cluster using statistical testing. Breaking the HF population into groups of similar patients revealed a clinically interpretable hierarchy of subgroups characterized by similar HF manifestation. Importantly, our methodology revealed well-known etiologies, risk factors, and comorbid conditions of HF (including ischemic heart disease, aortic valve disease, atrial fibrillation, congenital heart disease, various cardiomyopathies, obesity, hypertension, diabetes, and chronic kidney disease) and yielded additional insights into the details of each HF subgroup’s clinical manifestation of HF. Our approach is entirely hypothesis free and can therefore be readily applied for discovery of novel insights in alternative diseases or patient populations.
COG5 variants lead to complex early onset retinal degeneration, upregulation of PERK and DNA damage
Authors: Tabbarah Sami , Tavares Erika , Charish Jason , Vincent Ajoy , Paterson Andrew , Di Scipio Matteo , Yin Yue , Mendoza-Londono Roberto , Maynes Jason , Heon Elise , Monnier Philippe P. 
Published: December 2020

AbstractLeber congenital amaurosis (LCA), a form of autosomal recessive severe early-onset retinal degeneration, is an important cause of childhood blindness. This may be associated with systemic features or not. Here we identified COG5 compound-heterozygous variants in patients affected with a complex LCA phenotype associated with microcephaly and skeletal dysplasia. COG5 is a component of the COG complex, which facilitates retrograde Golgi trafficking; if disrupted this can result in protein misfolding. To date, variants in COG5 have been associated with a distinct congenital disorder of glycosylation (type IIi) and with a variant of Friedreich’s ataxia. We show that COG5 variants can also result in fragmentation of the Golgi apparatus and upregulation of the UPR modulator, PKR-like endoplasmic reticulum kinase (PERK). In addition, upregulation of PERK induces DNA damage in cultured cells and in murine retina. This study identifies a novel role for COG5 in maintaining ER protein homeostasis and that disruption of that role results in activation of PERK and early-onset retinal degeneration, microcephaly and skeletal dysplasia. These results also highlight the importance of the UPR pathway in early-onset retinal dystrophy and as potential therapeutic targets for patients.
Increased incarceration rates drive growing tuberculosis burden in prisons and jeopardize overall tuberculosis control in Paraguay
Authors: Sequera Víctor Guillermo , Aguirre Sarita , Estigarribia Gladys , Cellamare Matteo , Croda Julio , Andrews Jason R. , Martinez Leonardo , García-Basteiro Alberto L. 
Published: December 2020

AbstractIncarcerated populations are at high-risk to develop tuberculosis (TB), however their impact on the population-level tuberculosis epidemic has been scarcely studied. We aimed to describe the burden and trends of TB among incarcerated populations over time in Paraguay, its clinical and epidemiological differences and the population attributable fraction. This is an observational, descriptive study including all TB cases notified to the National TB control Program in Paraguay during the period 2009–2018. We also used case registries of prisoners diagnosed with tuberculosis from the Minister of Justice. The population attributable fraction of TB in the community due to incarcerated cases was estimated through Levin’s formula. The characteristics of TB cases in and outside of prison were compared as well as the characteristics of TB in prisons were modified over time. During 2009–2018, 2764 (9.7%) of the 28,534 TB reported cases in Paraguay occurred in prisons. The number of prisoners in Paraguay increased from 6258 in 2009 to 14,627 in 2018 (incarceration rate, 101 to 207 per 100,000 persons) while the number of TB cases among prisoners increased by 250% (n = 192 in 2009 versus n = 480 in 2018). The annual TB notification rate among male prisoners was 3218 and 3459 per 100,000 inmates in 2009 and 2018, respectively. The percentage of all TB cases occurring among prisoners increased from 7.1% in 2009 to 14.5% in 2018. The relative risk of TB in prisons compared to community was 70.3 (95% CI, 67.7–73.1); the overall population attributable risk was 9.5%. Among the 16 penitentiary centers in the country, two of them—Tacumbú (39.0%) and Ciudad del Este (23.3%)—represent two thirds of all TB cases in prisons. TB among inmates is predominantly concentrated in those 20–34 years old (77.3% of all), twice the percentage of cases for the same age group outside of prison. Our findings show that the TB epidemic in prisons represents one of the most important challenges for TB control in Paraguay, especially in the country’s largest cities. Appropriate TB control measures among incarcerated populations are needed and may have substantial impact on the overall TB burden in the country.
Dynamic response of cerebral blood flow to insulin-induced hypoglycemia
Authors: McManus Ruth , Ioussoufovitch Seva , Froats Elizabeth , St Lawrence Keith , Van Uum Stan , Diop Mamadou 
Published: December 2020

AbstractThe dynamics of cerebral blood flow (CBF) at the onset of hypoglycemia may play a key role in hypoglycemia unawareness; however, there is currently a paucity of techniques that can monitor adult CBF with high temporal resolution. Herein, we investigated the use of diffuse correlation spectroscopy (DCS) to monitor the dynamics of CBF during insulin-induced hypoglycemia in adults. Plasma glucose concentrations, cortisol levels, and changes in CBF were measured before and during hypoglycemia in 8 healthy subjects. Cerebral blood flow increased by 42% following insulin injection with a delay of 17 ± 10 min, while the onset of hypoglycemia symptoms was delayed by 24 ± 11 min. The findings suggest that the onset of CBF increments precedes the appearance of hypoglycemia symptoms in nondiabetic subjects with normal awareness to hypoglycemia, and DCS could be a valuable tool for investigating the role of CBF in hypoglycemia unawareness.