bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antisense oligonucleotides as a potential treatment for brain deficits observed in myotonic dystrophy type 1
Authors: Ait Benichou Siham , Jauvin Dominic , De Serres-Bérard Thiéry , Pierre Marion , Ling Karen K. , Bennett C. Frank , Rigo Frank , Gourdon Genevieve , Chahine Mohamed , Puymirat Jack 
Published: January 2022

AbstractMyotonic dystrophy, or dystrophia myotonica type 1 (DM1), is a multi-systemic disorder and is the most common adult form of muscular dystrophy. It affects not only muscles but also many organs, including the brain. Cerebral impairments include cognitive deficits, daytime sleepiness, and loss of visuospatial and memory functions. The expression of mutated transcripts with CUG repeats results in a gain of toxic mRNA function. The antisense oligonucleotide (ASO) strategy to treat DM1 brain deficits is limited by the fact that ASOs do not cross the blood–brain barrier after systemic administration, indicating that other methods of delivery should be considered. ASO technology has emerged as a powerful tool for developing potential new therapies for a wide variety of human diseases, and its potential has been proven in a recent clinical trial. Targeting DMPK mRNA in neural cells derived from human induced pluripotent stem cells obtained from a DM1 patient with the IONIS 486178 ASO abolished CUG-expanded foci, enabled nuclear redistribution of MBNL1/2, and corrected aberrant splicing. Intracerebroventricular injection of the IONIS 486178 ASO in DMSXL mice decreased the levels of mutant DMPK mRNAs by up to 70% throughout different brain regions. It also reversed behavioral abnormalities following neonatal administration. The present study indicated that the IONIS 486178 ASO targets mutant DMPK mRNAs in the brain and strongly supports the feasibility of a therapy for DM1 patients based on the intrathecal injection of an ASO.
Interaction data are identifiable even across long periods of time
Authors: Creţu Ana-Maria , Monti Federico , Marrone Stefano , Dong Xiaowen , Bronstein Michael , de Montjoye Yves-Alexandre 
Published: January 2022

AbstractFine-grained records of people’s interactions, both offline and online, are collected at large scale. These data contain sensitive information about whom we meet, talk to, and when. We demonstrate here how people’s interaction behavior is stable over long periods of time and can be used to identify individuals in anonymous datasets. Our attack learns the profile of an individual using geometric deep learning and triplet loss optimization. In a mobile phone metadata dataset of more than 40k people, it correctly identifies 52% of individuals based on their 2-hop interaction graph. We further show that the profiles learned by our method are stable over time and that 24% of people are still identifiable after 20 weeks. Our results suggest that people with well-balanced interaction graphs are more identifiable. Applying our attack to Bluetooth close-proximity networks, we show that even 1-hop interaction graphs are enough to identify people more than 26% of the time. Our results provide strong evidence that disconnected and even re-pseudonymized interaction data can be linked together making them personal data under the European Union’s General Data Protection Regulation.
Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome
Authors: Cervia Carlo , Zurbuchen Yves , Taeschler Patrick , Ballouz Tala , Menges Dominik , Hasler Sara , Adamo Sarah , Raeber Miro E. , Bächli Esther , Rudiger Alain , Stüssi-Helbling Melina , Huber Lars C. , Nilsson Jakob , Held Ulrike , Puhan Milo A. , Boyman Onur 
Published: January 2022

AbstractFollowing acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which – combined with age, history of asthma bronchiale, and five symptoms during primary infection – is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.
The evolution of mechanisms to produce phenotypic heterogeneity in microorganisms
Authors: Cooper Guy Alexander , Liu Ming , Peña Jorge , West Stuart Andrew 
Published: January 2022

AbstractIn bacteria and other microorganisms, the cells within a population often show extreme phenotypic variation. Different species use different mechanisms to determine how distinct phenotypes are allocated between individuals, including coordinated, random, and genetic determination. However, it is not clear if this diversity in mechanisms is adaptive—arising because different mechanisms are favoured in different environments—or is merely the result of non-adaptive artifacts of evolution. We use theoretical models to analyse the relative advantages of the two dominant mechanisms to divide labour between reproductives and helpers in microorganisms. We show that coordinated specialisation is more likely to evolve over random specialisation in well-mixed groups when: (i) social groups are small; (ii) helping is more “essential”; and (iii) there is a low metabolic cost to coordination. We find analogous results when we allow for spatial structure with a more detailed model of cellular filaments. More generally, this work shows how diversity in the mechanisms to produce phenotypic heterogeneity could have arisen as adaptations to different environments.
Heterotrimeric Gq proteins act as a switch for GRK5/6 selectivity underlying β-arrestin transducer bias
Authors: Kawakami Kouki , Yanagawa Masataka , Hiratsuka Suzune , Yoshida Misaki , Ono Yuki , Hiroshima Michio , Ueda Masahiro , Aoki Junken , Sako Yasushi , Inoue Asuka 
Published: January 2022

AbstractSignaling-biased ligands acting on G-protein-coupled receptors (GPCRs) differentially activate heterotrimeric G proteins and β-arrestins. Although a wealth of structural knowledge about signaling bias at the GPCR level exists (preferential engagement of a specific transducer), little is known about the bias at the transducer level (different functions mediated by a single transducer), partly due to a poor understanding of GPCR kinase (GRK)-mediated GPCR phosphorylation. Here, we reveal a unique role of the Gq heterotrimer as a determinant for GRK-subtype selectivity that regulates subsequent β-arrestin conformation and function. Using the angiotensin II (Ang II) type-1 receptor (AT1R), we show that β-arrestin recruitment depends on both GRK2/3 and GRK5/6 upon binding of Ang II, but solely on GRK5/6 upon binding of the β-arrestin-biased ligand TRV027. With pharmacological inhibition or genetic loss of Gq, GRK-subtype selectivity and β-arrestin functionality by Ang II is shifted to those of TRV027. Single-molecule imaging identifies relocation of AT1R and GRK5, but not GRK2, to an immobile phase under the Gq-inactive, AT1R-stimulated conditions. These findings uncover a previously unappreciated Gq-regulated mechanism that encodes GRK-subtype selectivity and imparts distinct phosphorylation-barcodes directing downstream β-arrestin functions.
Coding and regulatory variants are associated with serum protein levels and disease
Authors: Emilsson Valur , Gudmundsdottir Valborg , Gudjonsson Alexander , Jonmundsson Thorarinn , Jonsson Brynjolfur G. , Karim Mohd A. , Ilkov Marjan , Staley James R. , Gudmundsson Elias F. , Launer Lenore J. , Lindeman Jan H. , Morton Nicholas M. , Aspelund Thor , Lamb John R. , Jennings Lori L. , Gudnason Vilmundur 
Published: January 2022

AbstractCirculating proteins can be used to diagnose and predict disease-related outcomes. A deep serum proteome survey recently revealed close associations between serum protein networks and common disease. In the current study, 54,469 low-frequency and common exome-array variants were compared to 4782 protein measurements in the serum of 5343 individuals from the AGES Reykjavik cohort. This analysis identifies a large number of serum proteins with genetic signatures overlapping those of many diseases. More specifically, using a study-wide significance threshold, we find that 2021 independent exome array variants are associated with serum levels of 1942 proteins. These variants reside in genetic loci shared by hundreds of complex disease traits, highlighting serum proteins’ emerging role as biomarkers and potential causative agents of a wide range of diseases.
A non-catalytic herpesviral protein reconfigures ERK-RSK signaling by targeting kinase docking systems in the host
Authors: Alexa Anita , Sok Péter , Gross Fridolin , Albert Krisztián , Kobori Evan , Póti Ádám L. , Gógl Gergő , Bento Isabel , Kuang Ersheng , Taylor Susan S. , Zhu Fanxiu , Ciliberto Andrea , Reményi Attila 
Published: January 2022

AbstractThe Kaposi’s sarcoma associated herpesvirus protein ORF45 binds the extracellular signal-regulated kinase (ERK) and the p90 Ribosomal S6 kinase (RSK). ORF45 was shown to be a kinase activator in cells but a kinase inhibitor in vitro, and its effects on the ERK-RSK complex are unknown. Here, we demonstrate that ORF45 binds ERK and RSK using optimized linear binding motifs. The crystal structure of the ORF45-ERK2 complex shows how kinase docking motifs recognize the activated form of ERK. The crystal structure of the ORF45-RSK2 complex reveals an AGC kinase docking system, for which we provide evidence that it is functional in the host. We find that ORF45 manipulates ERK-RSK signaling by favoring the formation of a complex, in which activated kinases are better protected from phosphatases and docking motif-independent RSK substrate phosphorylation is selectively up-regulated. As such, our data suggest that ORF45 interferes with the natural design of kinase docking systems in the host.
Regional excess mortality during the 2020 COVID-19 pandemic in five European countries
Authors: Konstantinoudis Garyfallos , Cameletti Michela , Gómez-Rubio Virgilio , Gómez Inmaculada León , Pirani Monica , Baio Gianluca , Larrauri Amparo , Riou Julien , Egger Matthias , Vineis Paolo , Blangiardo Marta 
Published: January 2022

AbstractThe impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015–2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15–20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Here, we show that acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.
Selective transport of water molecules through interlayer spaces in graphite
Authors: Saini Lalita , Nemala Siva Sankar , Rathi Aparna , Kaushik Suvigya , Kalon Gopinadhan 
Published: January 2022

AbstractInterlayer space in graphite is impermeable to ions and molecules, including protons. Its controlled expansion would find several applications in desalination, gas purification, high-density batteries, etc. In the past, metal intercalation has been used to modify graphitic interlayer spaces; however, resultant intercalation compounds are unstable in water. Here, we successfully expanded graphite interlayer spaces by intercalating aqueous KCl ions electrochemically. Our spectroscopy studies provide clear evidence for cation-π interactions explaining the stability of the devices, though weak anion-π interactions were also detectable. The water conductivity shows several orders of enhancement when compared to unintercalated graphite. Water evaporation experiments further confirm the high permeation rate. There is weak ion permeation through interlayer spaces, up to the highest chloride concentration of 1 M, an indication of sterically limited transport. In these very few transported ions, we observe hydration energy-dependent selectivity between salt ions. These strongly suggest a soft ball model of steric exclusion, which is rarely reported. These findings improve our understanding of molecular and ionic transport at the atomic scale.
General synthesis of ultrafine metal oxide/reduced graphene oxide nanocomposites for ultrahigh-flux nanofiltration membrane
Authors: Zhang Wanyu , Xu Hai , Xie Fei , Ma Xiaohua , Niu Bo , Chen Mingqi , Zhang Hongyu , Zhang Yayun , Long Donghui 
Published: January 2022

AbstractGraphene-based membranes have great potential to revolutionize nanofiltration technology, but achieving high solute rejections at high water flux remains extremely challenging. Herein, a family of ultrafine metal oxide/reduced graphene oxide (rGO) nanocomposites are synthesized through a heterogenous nucleation and diffusion-controlled growth process for dye nanofiltration. The synthesis is based on the utilization of oxygen functional groups on GO surface as preferential active sites for heterogeneous nucleation, leading to the formation of sub-3 nm size, monodispersing as well as high-density loading of metal oxide nanoparticles. The anchored ultrafine nanoparticles could inhibit the wrinkling of the rGO nanosheet, forming highly stable colloidal solutions for the solution processing fabrication of nanofiltration membranes. By functioning as pillars, the nanoparticles remarkably increase both vertical interlayer spacing and lateral tortuous paths of the rGO membranes, offering a water permeability of 225 L m−2h−1bar−1and selectivity up to 98% in the size-exclusion separation of methyl blue.
Machine learning of superconducting critical temperature from Eliashberg theory
Authors: Xie S. R. , Quan Y. , Hire A. C. , Deng B. , DeStefano J. M. , Salinas I. , Shah U. S. , Fanfarillo L. , Lim J. , Kim J. , Stewart G. R. , Hamlin J. J. , Hirschfeld P. J. , Hennig R. G. 
Published: January 2022

AbstractThe Eliashberg theory of superconductivity accounts for the fundamental physics of conventional superconductors, including the retardation of the interaction and the Coulomb pseudopotential, to predict the critical temperature Tc. McMillan, Allen, and Dynes derived approximate closed-form expressions for the critical temperature within this theory, which depends on the electron–phonon spectral function α2F(ω). Here we show that modern machine-learning techniques can substantially improve these formulae, accounting for more general shapes of the α2F function. Using symbolic regression and the SISSO framework, together with a database of artificially generated α2F functions and numerical solutions of the Eliashberg equations, we derive a formula for Tc that performs as well as Allen–Dynes for low-Tc superconductors and substantially better for higher-Tc ones. This corrects the systematic underestimation of Tc while reproducing the physical constraints originally outlined by Allen and Dynes. This equation should replace the Allen–Dynes formula for the prediction of higher-temperature superconductors.
A capillary electrophoresis-based multiplex PCR assay for expanded carrier screening in the eastern Han Chinese population
Authors: Hu Ping , Tan Jianxin , Yu Feng , Shao Binbin , Zhang Fang , Zhang Jingjing , Lin Yingchun , Tao Tao , Jiang Lili , Jiang Zhengwen , Xu Zhengfeng 
Published: January 2022

AbstractExpanded carrier screening, a type of reproductive genetic testing for couples, has gained tremendous popularity for assessing the risk of passing on certain genetic conditions to offspring. Here, a carrier screening assay for 448 pathogenic variants was developed using capillary electrophoresis-based multiplex PCR technology. The capillary electrophoresis-based multiplex PCR assay achieved a sensitivity, specificity, and accuracy of 97.4%, 100%, and 99.6%, respectively, in detecting the specific variants. Among the 1915 couples (3830 individuals), 708 individuals (18.5%) were identified as carriers for at least one condition. Of the 708 carriers, 633 (89.4%) were heterozygous for one condition, 71 (10.0%) for two disorders, 3 (0.4%) for three disorders, and 1 (0.1%) for four disorders. Meanwhile, 30 (1.57%) couples were identified as at‐risk couples. This study describes an inexpensive and effective method for expanded carrier screening. The simplicity and accuracy of this approach will facilitate the clinical implementation of expanded carrier screening.
Marine Vibrio spp. protect carbon steel against corrosion through secreting extracellular polymeric substances
Authors: Gao Yu , Zhang Mingxing , Fan Yongqiang , Li Zhong , Cristiani Pierangela , Chen Xiaobo , Xu Dake , Wang Fuhui , Gu Tingyue 
Published: January 2022

AbstractThe protection of marine materials against corrosion using marine bacterial biofilms is a promising strategy. However, little is known about the mechanisms of this attractive corrosion prevention method. In this work, the corrosion behaviors of X80 carbon steel (CS) in the presence of three different marine Vibrio species were studied. The results demonstrated that all the three Vibrio spp. displayed significant corrosion protection with a weight loss reduction of up to 68%. Moreover, their corrosion prevention performance was tightly related to their abilities to form biofilms, which was in the order of Vibrio sp. EF187016 > Vibrio alginolyticus > Vibrio parahaemolyticus. To further investigate the corrosion prevention mechanism caused by marine biofilms, the extracellular polymeric substances (EPS) of Vibrio sp. EF187016 was extracted and added to 3.5 wt% NaCl for abiotic corrosion testing. The results suggested that the EPS inhibited corrosion, which means EPS can play a significant role in corrosion protection by biofilm.
Non-linear rheology reveals the importance of elasticity in meat and meat analogues
Authors: Schreuders Floor K. G. , Sagis Leonard M. C. , Bodnár Igor , Boom Remko M. , van der Goot Atze Jan 
Published: January 2022

AbstractThe interest in plant-based meat analogues as an alternative to meat is currently growing. Rheological benchmarking is used to reveal how closely meat analogues resemble the original meat products. Texture maps and dissipation colour schemes were used to reveal similarities in and differences between rheological responses of meat and meat analogues (especially chicken analogues). Under heating, meat analogues differ in terms of their lower elasticity compared with heated meat. The changes caused by heating meat and meat analogues were different as well. Heating of meat resulted in a tougher and more elastic material, while heating has a minor effect on meat analogues. Future developments should therefore focus on routes to create more elasticity and possibly allow heating effects on texture to mimic meat characteristics even better.
A novel analysis of heat transfer in the nanofluid composed by nanodimaond and silver nanomaterials: numerical investigation
Authors: Adnan  , Khan Umar , Ahmed Naveed , Mohyud-Din Syed Tauseef , Alsulami M. D. , Khan Ilyas 
Published: January 2022

AbstractThe investigation of thermal performance in the nanofluids for unsteady boundary layer flow by considering the impacts of suction/injection is a significant research area in the field of fluid dynamics. This flow situation is broadly used in aerodynamics and space sciences as well. The model is formulated for ND-H2O and Ag-H2O nanofluids and then tackled numerically and captured the dynamics of the nanofluids under the multiple flow parameters. From the results, it is investigated that both ND-H2O and Ag-H2O have high thermal performance characteristics. However, higher heat transfer performance is observed for Ag based nanofluid. Further, a graphical and tabular comparison under certain assumptions is provided to authenticate the analysis.
Vaccination of mice with hybrid protein containing Exotoxin S and PcrV with adjuvants alum and MPL protects Pseudomonas aeruginosa infections
Authors: Asadi Karam Mohammad Reza , Badmasti Farzad , Ahmadi Khadijeh , Habibi Mehri 
Published: January 2022

AbstractPseudomonas aeruginosa as a common pathogen causing urinary tract infections (UTIs) has been resistant to different antibiotics and developing an effective vaccine can be an alternative strategy. In the present study, the immunogenicity and protection efficacy of formulations composed of a hybrid protein composed of P. aeruginosa V-antigen (PcrV) and exoenzyme S (ExoS) with alum and MPL were evaluated. The hybrid protein could increase the specific systemic and mucosal immune responses, as well as cellular responses as compared with control groups. Combining of alum or MPL adjuvant with the hybrid protein significantly improved the levels of IgG1, serum IgA, mucosal IgG, and IL-17 as compared to the ExoS.PcrV alone. After bladder challenge with a P. aeruginosa strain, the bacterial loads of bladder and kidneys were significantly decreased in mice received ExoS.PcrV admixed with alum and ExoS.PcrV admixed with MPL than controls. The present study indicated that immunization of mice with a hybrid protein composed of ExoS and PcrV could induce multifactorial immune responses and opsonize the bacteria and decrease the viable bacterial cells. Because P. aeruginosa have caused therapeutic challenges worldwide, our study proposed ExoS.PcrV + alum and ExoS.PcrV + MPL as promising candidates for the prevention of infections caused by P. aeruginosa.
Aptamer based point of care diagnostic for the detection of food allergens
Authors: Stidham Sarah , Villareal Valerie , Chellappa Vasant , Yoder Lucas , Alley Olivia , Shreffler Wayne , Spergel Jonathan , Fleischer David , Sampson Hugh , Gilboa-Geffen Adi 
Published: January 2022

AbstractAptamers, due to their small size, strong target affinity, and ease of chemical modification, are ideally suited for molecular detection technologies. Here, we describe successful use of aptamer technology in a consumer device for the detection of peanut antigen in food. The novel aptamer-based protein detection method is robust across a wide variety of food matrices and sensitive to peanut protein at concentrations as low as 12.5 ppm (37.5 µg peanut protein in the sample). Integration of the assay into a sensitive, stable, and consumer friendly portable device will empower users to easily and quickly assess the presence of peanut allergens in foods before eating. With many food reactions occurring outside the home, the type of technology described here has significant potential to improve lives for children and families.