bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic underpinning of an inside–out concept for autoimmunity in multiple sclerosis
Authors: ’t Hart Bert A. , Luchicchi Antonio , Schenk Geert J. , Stys Peter K. , Geurts Jeroen J. G. 
Published: June 2021

AbstractThe neuroinflammatory disease multiple sclerosis is driven by autoimmune pathology in the central nervous system. However, the trigger of the autoimmune pathogenic process is unknown. MS models in immunologically naïve, specific‐pathogen‐free bred rodents support an exogenous trigger, such as an infection. The validity of this outside–in pathogenic concept for MS has been frequently challenged by the difficulty to translate pathogenic concepts developed in these models into effective therapies for the MS patient. Studies in well‐validated non‐human primate multiple sclerosis models where, just like in humans, the autoimmune pathogenic process develops from an experienced immune system trained by prior infections, rather support an endogenous trigger. Data reviewed here corroborate the validity of this inside–out pathogenic concept for multiple sclerosis. They also provide a plausible sequence of events reminiscent of Wilkin’s primary lesion theory: (i) that autoimmunity is a physiological response of the immune system against excess antigen turnover in diseased tissue (the primary lesion) and (ii) that individuals developing autoimmune disease are (genetically predisposed) high responders against critical antigens. Data obtained in multiple sclerosis brains reveal the presence in normally appearing white matter of myelinated axons where myelin sheaths have locally dissociated from their enwrapped axon (i.e., blistering). The ensuing disintegration of axon–myelin units potentially causes the excess systemic release of post‐translationally modified myelin. Data obtained in a unique primate multiple sclerosis model revealed a core pathogenic role of T cells present in the normal repertoire, which hyper‐react to post‐translationally modified (citrullinated) myelin–oligodendrocyte glycoprotein and evoke clinical and pathological aspects of multiple sclerosis.
Multi‐Level Control of Conductive Filament Evolution and Enhanced Resistance Controllability of the Cu‐Cone Structure Embedded Conductive Bridge Random Access Memory
Authors: Kim Hae Jin , Kim Jihun , Park Tae Gyun , Yoon Jung Ho , Hwang Cheol Seong 
Published: June 2021

AbstractMemristor is considered as one of the key components of neuromorphic hardware aiming to overcome the limitations of classical von Neumann computers, but the continuous control of the device conduction remains a challenge. Random and stochastic dynamics of weak conducting filaments (CF) hinder the precise control of the resistance states, particularly in the conductive bridge random access memory (CBRAM). The problem of random and stochastic resistive switching of the Cu‐based CBRAM is largely mitigated by inserting the Cu‐cone as a cation source into the memory cell (Cu‐cone device). The electric field concentrated on the Cu‐cone induces stronger CF with a limited number near the tip region, making the device feature distinctive from the planar Cu CBRAM. The Cu‐cone device exhibits enhanced resistance controllability attributed to the well‐controlled CF, improved switching reliability improvement, and multiple intermediate resistance states. Such features are used to explore its usefulness as an artificial synapse, where fluent potentiation and depression can be achieved using voltage pulses. Further research is still required to emulate the artificial synapses fully, but the feasibility is presented in this work by exploiting the similarities between the Cu cations in the CBRAM device and the Ca2+dynamics in a biological synapse.
L‐carnitine supplementation for muscle weakness and fatigue in children with neurofibromatosis type 1: A Phase 2a clinical trial
Authors: Vasiljevski Emily R. , Burns Joshua , Bray Paula , Donlevy Gabrielle , Mudge Anita J. , Jones Kristi J. , Summers Matthew A. , Biggin Andrew , Munns Craig F. , McKay Marnee J. , Baldwin Jennifer N. , Little David G. , Schindeler Aaron 
Published: June 2021

AbstractReduced muscle tone, muscle weakness, and physical fatigue can impact considerably on quality of life for children with neurofibromatosis type 1 (NF1). Human muscle biopsies and mouse models of NF1 deficiency in muscle show intramyocellular lipid accumulation, and preclinical data have indicated that L‐carnitine supplementation can ameliorate this phenotype. The aim of this study is to examine whether daily L‐carnitine supplementation is safe and feasible, and will improve muscle strength and reduce fatigue in children with NF1. A 12‐week Phase 2a trial was conducted using 1000 mg daily oral levocarnitine tartrate supplementation. Recruited children were between 8 and 12 years old with a clinical diagnosis of NF1, history of muscle weakness and fatigue, and naïve to L‐carnitine. Primary outcomes were safety (self‐reporting, biochemical testing) and compliance. Secondary outcomes included plasma acylcarnitine profiles, functional measures (muscle strength, long jump, handwriting speed, 6‐minute‐walk test [6MWT]), and parent‐reported questionnaires (PedsQL™, CBCL/6–18). Six children completed the trial with no self‐reported adverse events. Biochemical tests for kidney and liver function were normal, and the average compliance was 95%. Plasma acylcarnitine levels were low, but within a range not clinically linked to carnitine deficiency. For strength measures, there was a mean 53% increase in dorsiflexion strength (95% confidence interval [CI] 8.89–60.75; p = 0.02) and mean 66% increase in plantarflexion strength (95% CI 12.99–134.1; p = 0.03). In terms of muscle performance, there was a mean 10% increase in long jump distance (95% CI 2.97–16.03; p = 0.01) and 6MWT distance (95% CI 5.88–75.45; p = 0.03). Comparison with the 1000 Norms Project data showed a significant improvement in Z‐score for all of these measures. Parent reports showed no negative impact on quality of life, and the perceived benefits led to the majority of individuals remaining on L‐carnitine after the study. Twelve weeks of L‐carnitine supplementation is safe and feasible in children with NF1, and a Phase 3 trial should confirm the efficacy of treatment.
Dominance rank, female choice, and reproductive success in semi‐free ranging adult male Japanese macaques (Macaca fuscata)
Authors: Gartland Kylen N. , Biggs Nichole , Shreeve Caitlin M. , White Frances J. 
Published: June 2021

AbstractThe assumed evolutionary advantage of dominance is increased reproductive success. However, the efficacy of dominance as a mating strategy may be interrupted by any number of variables including female choice, estrous synchrony, and mating by non‐troop males. In Japanese macaques (Macaca fuscata), there is evidence both for and against dominance as conferring reproductive success for adult males, with many discussions pointing to the importance of female choice in governing reproductive success in certain populations. In this study, we aimed to evaluate dominance‐basedversusfemale choice‐based male behavioral strategies and their impact on reproductive success. This study was conducted on a group of Japanese macaques at the Oregon National Primate Research Center. We collected a total of 512 h of behavioral data across two summer study periods in 2018 and 2019. We conducted 15‐min focal follows with 1‐min instantaneous scans on 17 adult males. Reproductive data were available from genetic records. Using principal components analysis (PCA), we identified males that cluster according to similar behavioral strategies. We then used analysis of variance (ANOVA) and non‐parametric ANOVA on ranks to ascertain significant variation in rank and reproductive success between clusters. We found that males that clustered based on high directed aggression held higher rank than less‐aggressive male clusters (F = 27.21,df = 4,p < .0001). However, less aggressive male clusters had higher reproductive success (F = 3.50,df = 4,p = .04). There was no variation between affiliative clusters in reproductive success (F = 1.77,df = 3,p = .15). The highly aggressive strategy is effective for attaining high rank, but only resulted in high reproductive success for a single male which likely necessitates alternative strategies. We suggest the operation of female choice within this population, with females preferentially mating with males who are not only affiliative but also less aggressive.
The Electronic Metal–Support Interaction Directing the Design of Single Atomic Site Catalysts: Achieving High Efficiency Towards Hydrogen Evolution
Authors: Yang Jiarui , Li Wen‐Hao , Tan Shengdong , Xu Kaini , Wang Yu , Wang Dingsheng , Li Yadong 
Published: June 2021

AbstractIt is still of great difficulty to develop the non‐platinum catalyst with high catalytic efficiency towards hydrogen evolution reaction via the strategies till now. Therefore, it is necessary to develop the new methods of catalyst designing. Here, we put forward the catalyst designed by the electronic metal–support interaction (EMSI), which is demonstrated to be a reliable strategy to find out the high‐efficiency catalyst. We carried out the density functional theory calculation first to design the proper EMSI of the catalyst. We applied the model of M1‐M2‐X (X=C, N, O) during the calculation. Among the catalysts we chose, the EMSI of Rh1TiC, with the active sites of Rh1‐Ti2C2, is found to be the most proper one for HER. The electrochemical experiment further demonstrated the feasibility of the EMSI strategy. The single atomic site catalyst of Rh1‐TiC exhibits higher catalytic efficiency than that of state‐of‐art Pt/C. It achieves a small overpotential of 22 mV and 86 mV at the at the current density of 10 mA cm−2 and 100 mA cm−2 in acid media, with a Tafel slope of 25 mV dec−1 and a mass activity of 54403.9 mA cm−2 mgRh−1 (vs. 192.2 mA cm−2 mgPt−1 of Pt/C). Besides, it also shows appealing advantage in energy saving compared with Pt/C (≈20 % electricity consuming decrease at 2 kA m−2) Therefore, we believe that the strategy of regulating EMSI can act as a possible way for achieving the high catalytic efficiency on the next step of SACs.
Chemically Stabilized DNA Barcodes for DNA‐Encoded Chemistry
Authors: Potowski Marco , Kunig Verena B. K. , Eberlein Lukas , Vakalopoulos Alexandros , Kast Stefan M. , Brunschweiger Andreas 
Published: June 2021

AbstractDNA‐encoded compound libraries are a widely used small molecule screening technology. One important aim in library design is the coverage of chemical space through structurally diverse molecules. Yet, the chemical reactivity of native DNA barcodes limits the toolbox of reactions for library design. Substituting the chemically vulnerable purines by 7‐deazaadenine, which exhibits tautomerization stability similar to natural adenine with respect to the formation of stable Watson–Crick pairs, yielded ligation‐competent, amplifiable, and readable DNA barcodes for encoded chemistry with enhanced stability against protic acid‐ and metal ion‐promoted depurination. The barcode stability allowed for straightforward translation of 16 exemplary reactions that included isocyanide multicomponent reactions, acid‐promoted Pictet–Spengler and Biginelli reactions, and metal‐promoted pyrazole syntheses on controlled pore glass‐coupled barcodes for diverse DEL design. The Boc protective group of reaction products offered a convenient handle for encoded compound purification.
Synthesis of novel benzimidazoles and benzothiazoles via furan‐2‐carboxaldehydes, o‐phenylenediamines, and 2‐aminothiophenol using Cu(II) Schiff‐base@SiO2 as a nanocatalyst
Authors: Sharghi Hashem , Mashhadi Elahe , Aberi Mahdi , Aboonajmi Jasem 
Published: June 2021

2‐(5‐Substituted phenyl)furan‐2‐carboxaldehyde derivatives were prepared by using an efficient copper(II) complex of tetradentate Schiff‐base ligand immobilized onto silica as a heterogeneous nanocatalyst [Cu(II) Schiff‐base@SiO2] (5.0 mol%) using anilines, sodium nitrite, and furan‐2‐carboxaldehyde. Furthermore, attractive di‐heteroaryl benzo‐fused systems such as benzimidazole and benzothiazole derivatives were synthesized using this nanocatalyst (5.0 mol%) via the reaction of o‐phenylenediamines and 2‐aminothiophenol with 2‐(5‐substituted phenyl)furan‐2‐carboxaldehydes in EtOH. The catalyst was characterized by Fourier transform infrared (FT‐IR), field emission scanning electron microscope (FESEM), energy‐dispersive X‐ray spectroscopy (EDX), X‐ray powder diffraction (XRD), and inductively coupled plasma (ICP) techniques. The advantages of the present catalytic system are short reaction times, mild conditions, good to excellent yields, and low amount of nanocatalyst. Moreover, to the best of our knowledge, this is the first time of using the same catalyst in two steps including synthesis of 2‐(5‐substituted phenyl)furan‐2‐carboxaldehyde and benzimidazole or benzothiazole derivatives. In addition, the synthesized catalyst was recycled very well and reused several times without significant loss of its catalytic activity.
Atlantic salmon in a rapidly changing environment—Facing the challenges of reduced marine survival and climate change
Authors: Thorstad Eva B. , Bliss Doug , Breau Cindy , Damon‐Randall Kim , Sundt‐Hansen Line E. , Hatfield Emma M.C. , Horsburgh Grant , Hansen Heidi , Maoiléidigh Niall Ó. , Sheehan Timothy , Sutton Stephen G. 
Published: June 2021

Abstract

Atlantic salmon populations have declined in recent decades. Many of the threats to the species during its freshwater and coastal residency periods are known, and management approaches are available to mitigate them. The global scale of climate change and altered ocean ecosystems make these threats more difficult to address.
Managers need to be aware that promoting strong, healthy, and resilient wild populations migrating from rivers is the optimal approach currently to reduce the impacts of changing ecosystems and low marine survival. We argue that a fundamental strategy should be to ensure that the highest number of wild smolts in the best condition leave from rivers and coastal areas to the ocean. There is great scope for water quality, river regulation, migration barriers, and physical river habitat improvements.
Maintenance of genetic integrity and diversity of wild populations by eliminating interbreeding with escaped farmed salmon, eliminating poorly planned stocking, and reducing impacts that reduce population sizes to dangerously low levels will support the ability of Atlantic salmon to adapt to changing environments. Reducing the impacts from aquaculture and other human activities in coastal areas can greatly increase marine survival in affected areas.
As most of the threats to wild salmon are the result of human activities, a focus on human dimensions and improved communication, from scientific and management perspectives, needs to be increasingly emphasized. When political and social will are coupled with adequate resources, managers often have the tools to mitigate many of the threats to wild salmon.
Optimal output tracking of switched Boolean networks
Authors: Chen Yuzhi , Sun Pengfei , Sun Tao , Alassafi Madini O. , Ahmad Adil M. 
Published: June 2021

AbstractIn this paper, the optimal output tracking problem for a class of switched Boolean networks is investigated by using a graph‐theoretical method. Firstly, by using the semitensor product of matrices, the algebraic equation of switched Boolean networks is formulated, and then by utilizing the concepts of set stabilization and switching invariant set, the trackability of a switched Boolean network is judged. Furthermore, the optimal switching sequence for optimal output tracking of switched Boolean networks is designed by using the heap‐optimized Dijkstra algorithm and the constructed optimal state transition graph, which enables the system to track a given reference signal with the minimum cost. Finally, a numerical example is given to demonstrate the validity of the presented results.
The first case of mosaic MNX1 mutation in an adult female with features of Currarino syndrome
Authors: Romano Ferruccio , De Marco Patrizia , Ognibene Marzia , Di Duca Marco , Baldassari Simona , Pavanello Marco , Piatelli Gianluca , Zara Federico , Capra Valeria 
Published: June 2021

AbstractBackgroundCurrarino syndrome (CS) is a rare genetic condition characterized by the association of three major clinical signs: anorectal malformation (ARM), sacro‐coccygeal bone defects, and presacral mass. Different kinds of ARM can be present such as anteriorly placed anus, imperforate anus, anorectal stenosis, rectal duplication, and fistulae. The presacral mass can be a benign teratoma, a dermoid or neurenteric cyst, anterior meningocele or hamartoma. Females are more frequently affected and usually present with associated gynecologic and urinary tract problems. CS is considered an autosomal dominant trait, with reduced penetrance and variable expressivity. CS is associated with mutations in the MNX1 gene (motor neuron and pancreas homeobox‐1, previously known as HLXB9) mapped to chromosome 7q36. Heterozygous loss‐of‐function mutations in the coding sequence of MNX1 gene have been reported in nearly all familial CS cases and in approximately 30% of CS sporadic patients.CaseHere, we present the case of a woman with features of CS carrying a mosaic mutation in the coding region of MNX1 gene. This is the only reported case of a CS diagnosis in which the mutation is present in less than 50% of cells.ConclusionThe lower detection rate of MNX1 mutations in sporadic cases could similarly be explained by somatic mosaicism, mutations occurring outside the coding regions, or genetic heterogeneity.
Training biochemistry students in experimental developmental biology: Induction of cardia bifida formation in the chick embryo
Authors: Palmquist‐Gomes Paul , Pérez‐Pomares José María , Guadix Juan Antonio 
Published: June 2021

AbstractA high variety of experimental model organisms have been used in developmental biology practical lectures. The work with developing embryos is crucial to make students aware of the multiple biological phenomena underlying normal animal embryogenesis and morphogenesis and represent a unique experimental platform to analyze the impact of molecular signaling in the regulation of all these processes. In particular, Biochemistry undergraduate students enjoy both practical and theoretical lectures on the molecular mechanisms of embryonic development, as that allows them for the integration of crucial molecular concepts (e.g. signaling and signal transduction mechanisms; molecular patterning of development) into the dynamic and progressive context of animal embryonic ontogenesis. Accordingly, it is important to carefully design practical laboratory lectures in developmental biology, as these are a unique pedagogical tools fostering the interests of the students in this subject. This study describes the design, implementation, and evaluation of a two‐session laboratory practical activity performed by Biochemistry undergraduate students at University of Málaga (Spain). In this practical activity, which takes advantage of the unique characteristics of the chick embryo, students learn how the vertebrate heart forms from the fusion of two bilateral‐symmetric cardiac progenitor pools under the guidance of the underlying endoderm. This cheap and easy practical laboratory activity provides relevant visual information on how experimental manipulations can severely influence anatomical form during organ development, as well as an excellent experimental setting to test molecular regulation of morphogenesis in an ex vivo (ex ovo) context.
Sleep deprivation alters task‐related changes in functional connectivity of the frontal cortex: A near‐infrared spectroscopy study
Authors: Mukli Peter , Csipo Tamas , Lipecz Agnes , Stylianou Orestis , Racz Frigyes Samuel , Owens Cameron D. , Perry Jonathan W. , Tarantini Stefano , Sorond Farzaneh A. , Kellawan Jeremy M. , Purebl György , Yang Yuan , Sonntag William E. , Csiszar Anna , Ungvari Zoltan I. , Yabluchanskiy Andriy 
Published: June 2021

AbstractSleep deprivation (SD) is known to be associated with decreased cognitive performance; however, the underlying mechanisms are poorly understood. As interactions between distinct brain regions depend on mental state, functional brain networks established by these connections typically show a reorganization during task. Hence, analysis of functional connectivity (FC) could reveal the task‐related change in the examined frontal brain networks. Our objective was to assess the impact of SD on static FC in the prefrontal and motor cortices and find whether changes in FC correlate with changes in neuropsychological scores. Healthy young male individuals (n = 10, 27.6 ± 3.7 years of age) participated in the study. A battery of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and 48 channel functional near‐infrared spectroscopy (fNIRS) measurements were performed before and after 24 hr of SD. Network metrics were obtained by graph theoretical analysis using the fNIRS records in resting state and during finger‐tapping sessions. During task, SD resulted in a significantly smaller decrease in the number and strength of functional connections (characterizing FC) in the frontal cortex. Changes in the global connection strengths correlated with decreased performance in the paired association learning test. These results indicate a global impact of SD on functional brain networks in the frontal lobes.
DNAzyme‐Catalyzed Cellular Oxidative Stress Amplification for Pro‐protein Activation in Living Cells
Authors: Li Wenting , Liu Ji , Shao Leihou , Mao Lanqun , Wang Ming 
Published: June 2021

AbstractThe conditional control of protein function in response to the physiological change of cells is of great interest for studying protein function in biological settings and developing protein therapeutics. We report herein that catalase (CAT) DNAzyme can potentiate the generation of reactive oxygen species (ROS) in living cells by knocking down catalase expression, which could further activate a reactive oxygen species (ROS)‐responsive pro‐protein, RNase A‐NBC, in situ. Using an optimized lipid nanoparticle delivery system to simultaneously introduce CAT DNAzyme and RNase A‐NBC into cells, we show that the pro‐protein, RNase A‐NBC, could be activated in a significantly enhanced manner to prohibit tumor cell growth in different types of cancer cells. We believe the methodology of regulating pro‐protein activity using DNAzyme biocatalysis to differentiate intracellular environment could further be extended to other functional proteins, and even fundamental investigations in living systems to develop pro‐protein therapeutics.
Primary percutaneous coronary intervention of anomalous origin of a high take‐off of right coronary artery arising from ascending aorta with percutaneous cardiopulmonary support in acute myocardial infarction
Authors: Shimizu Takuya , Umetani Ken , Eguchi Miu 
Published: June 2021

AbstractCoronary angiography of high take‐off right coronary artery (RCA) arising from ascending aorta under percutaneous cardiopulmonary support may be more effective at the site distal to RCA ostium rather than proximal. Guide extension catheters (GECs) may be useful to strengthen backup of percutaneous coronary interventions (PCI) system and to contrast coronary lesions clearly during PCI of these RCAs.