bluuebunny/crossref_metadata_2025_split huggingface dataset:
FoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes
Authors: Miyoshi Goichi , Ueta Yoshifumi , Natsubori Akiyo , Hiraga Kou , Osaki Hironobu , Yagasaki Yuki , Kishi Yusuke , Yanagawa Yuchio , Fishell Gord , Machold Robert P. , Miyata Mariko 
Published: June 2021

AbstractAbnormalities in GABAergic inhibitory circuits have been implicated in the aetiology of autism spectrum disorder (ASD). ASD is caused by genetic and environmental factors. Several genes have been associated with syndromic forms of ASD, including FOXG1. However, when and how dysregulation of FOXG1 can result in defects in inhibitory circuit development and ASD-like social impairments is unclear. Here, we show that increased or decreased FoxG1 expression in both excitatory and inhibitory neurons results in ASD-related circuit and social behavior deficits in our mouse models. We observe that the second postnatal week is the critical period when regulation of FoxG1 expression is required to prevent subsequent ASD-like social impairments. Transplantation of GABAergic precursor cells prior to this critical period and reduction in GABAergic tone via Gad2 mutation ameliorates and exacerbates circuit functionality and social behavioral defects, respectively. Our results provide mechanistic insight into the developmental timing of inhibitory circuit formation underlying ASD-like phenotypes in mouse models.
Static-state particle fabrication via rapid vitrification of a thixotropic medium
Authors: Kim Sang Yup , Liu Shanliangzi , Sohn Sungwoo , Jacobs Jane , Shattuck Mark D. , O’Hern Corey S. , Schroers Jan , Loewenberg Michael , Kramer-Bottiglio Rebecca 
Published: June 2021

AbstractFunctional particles that respond to external stimuli are spurring technological evolution across various disciplines. While large-scale production of functional particles is needed for their use in real-life applications, precise control over particle shapes and directional properties has remained elusive for high-throughput processes. We developed a high-throughput emulsion-based process that exploits rapid vitrification of a thixotropic medium to manufacture diverse functional particles in large quantities. The vitrified medium renders stationary emulsion droplets that preserve their shape and size during solidification, and energetic fields can be applied to build programmed anisotropy into the particles. We showcase mass-production of several functional particles, including low-melting point metallic particles, self-propelling Janus particles, and unidirectionally-magnetized robotic particles, via this static-state particle fabrication process.
A global analysis of extreme coastal water levels with implications for potential coastal overtopping
Authors: Almar Rafael , Ranasinghe Roshanka , Bergsma Erwin W. J. , Diaz Harold , Melet Angelique , Papa Fabrice , Vousdoukas Michalis , Athanasiou Panagiotis , Dada Olusegun , Almeida Luis Pedro , Kestenare Elodie 
Published: June 2021

AbstractClimate change and anthropogenic pressures are widely expected to exacerbate coastal hazards such as episodic coastal flooding. This study presents global-scale potential coastal overtopping estimates, which account for not only the effects of sea level rise and storm surge, but also for wave runup at exposed open coasts. Here we find that the globally aggregated annual overtopping hours have increased by almost 50% over the last two decades. A first-pass future assessment indicates that globally aggregated annual overtopping hours will accelerate faster than the global mean sea-level rise itself, with a clearly discernible increase occurring around mid-century regardless of climate scenario. Under RCP 8.5, the globally aggregated annual overtopping hours by the end of the 21st-century is projected to be up to 50 times larger compared to present-day. As sea level continues to rise, more regions around the world are projected to become exposed to coastal overtopping.
Mechanism of genome instability mediated by human DNA polymerase mu misincorporation
Authors: Guo Miao , Wang Yina , Tang Yuyue , Chen Zijing , Hou Jinfeng , Dai Jingli , Wang Yudong , Wang Liangyan , Xu Hong , Tian Bing , Hua Yuejin , Zhao Ye 
Published: June 2021

AbstractPol μ is capable of performing gap-filling repair synthesis in the nonhomologous end joining (NHEJ) pathway. Together with DNA ligase, misincorporation of dGTP opposite the templating T by Pol μ results in a promutagenic T:G mispair, leading to genomic instability. Here, crystal structures and kinetics of Pol μ substituting dGTP for dATP on gapped DNA substrates containing templating T were determined and compared. Pol μ is highly mutagenic on a 2-nt gapped DNA substrate, with T:dGTP base pairing at the 3ʹ end of the gap. Two residues (Lys438 and Gln441) interact with T:dGTP and fine tune the active site microenvironments. The in-crystal misincorporation reaction of Pol μ revealed an unexpected second dGTP in the active site, suggesting its potential mutagenic role among human X family polymerases in NHEJ.
The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis
Authors: Teng Liu , Feng Yu Chen , Guo Su Tang , Wang Pei Lin , Qi Teng Fei , Yue Yi Meng , Wang Shi Xing , Zhang Sheng Nan , Tang Cai Xia , La Ting , Zhang Yuan Yuan , Zhao Xiao Hong , Gao Jin Nan , Wei Li Yuan , Zhang Didi , Wang Jenny Y. , Shi Yujie , Liu Xiao Ying , Li Jin Ming , Cao Huixia , Liu Tao , Thorne Rick F. , Jin Lei , Shao Feng-Min , Zhang Xu Dong 
Published: June 2021

AbstractGenomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.
Preventing post-surgical cardiac adhesions with a catechol-functionalized oxime hydrogel
Authors: Fujita Masaki , Policastro Gina M. , Burdick Austin , Lam Hillary T. , Ungerleider Jessica L. , Braden Rebecca L. , Huang Diane , Osborn Kent G. , Omens Jeffrey H. , Madani Michael M. , Christman Karen L. 
Published: June 2021

AbstractPost-surgical cardiac adhesions represent a significant problem during routine cardiothoracic procedures. This fibrous tissue can impair heart function and inhibit surgical access in reoperation procedures. Here, we propose a hydrogel barrier composed of oxime crosslinked poly(ethylene glycol) (PEG) with the inclusion of a catechol (Cat) group to improve retention on the heart for pericardial adhesion prevention. This three component system is comprised of aldehyde (Ald), aminooxy (AO), and Cat functionalized PEG mixed to form the final gel (Ald-AO-Cat). Ald-AO-Cat has favorable mechanical properties, degradation kinetics, and minimal swelling, as well as superior tissue retention compared to an initial Ald-AO gel formulation. We show that the material is cytocompatible, resists cell adhesion, and led to a reduction in the severity of adhesions in an in vivo rat model. We further show feasibility in a pilot porcine study. The Ald-AO-Cat hydrogel barrier may therefore serve as a promising solution for preventing post-surgical cardiac adhesions.
All-optical nonreciprocity due to valley polarization pumping in transition metal dichalcogenides
Authors: Guddala Sriram , Kawaguchi Yuma , Komissarenko Filipp , Kiriushechkina Svetlana , Vakulenko Anton , Chen Kai , Alù Andrea , M. Menon Vinod , Khanikaev Alexander B. 
Published: June 2021

AbstractNonreciprocity and nonreciprocal optical devices play a vital role in modern photonic technologies by enforcing one-way propagation of light. Here, we demonstrate an all-optical approach to nonreciprocity based on valley-selective response in transition metal dichalcogenides (TMDs). This approach overcomes the limitations of magnetic materials and it does not require an external magnetic field. We provide experimental evidence of photoinduced nonreciprocity in a monolayer WS2 pumped by circularly polarized (CP) light. Nonreciprocity stems from valley-selective exciton population, giving rise to nonlinear circular dichroism controlled by CP pump fields. Our experimental results reveal a significant effect even at room temperature, despite considerable intervalley-scattering, showing promising potential for practical applications in magnetic-free nonreciprocal platforms. As an example, here we propose a device scheme to realize an optical isolator based on a pass-through silicon nitride (SiN) ring resonator integrating the optically biased TMD monolayer.
Deep reinforcement learning for efficient measurement of quantum devices
Authors: Nguyen V. , Orbell S. B. , Lennon D. T. , Moon H. , Vigneau F. , Camenzind L. C. , Yu L. , Zumbühl D. M. , Briggs G. A. D. , Osborne M. A. , Sejdinovic D. , Ares N. 
Published: June 2021

AbstractDeep reinforcement learning is an emerging machine-learning approach that can teach a computer to learn from their actions and rewards similar to the way humans learn from experience. It offers many advantages in automating decision processes to navigate large parameter spaces. This paper proposes an approach to the efficient measurement of quantum devices based on deep reinforcement learning. We focus on double quantum dot devices, demonstrating the fully automatic identification of specific transport features called bias triangles. Measurements targeting these features are difficult to automate, since bias triangles are found in otherwise featureless regions of the parameter space. Our algorithm identifies bias triangles in a mean time of <30 min, and sometimes as little as 1 min. This approach, based on dueling deep Q-networks, can be adapted to a broad range of devices and target transport features. This is a crucial demonstration of the utility of deep reinforcement learning for decision making in the measurement and operation of quantum devices.
An epitope-specific chemically defined nanoparticle vaccine for respiratory syncytial virus
Authors: Zuniga Armando , Rassek Oliver , Vrohlings Melissa , Marrero-Nodarse Aniebrys , Moehle Kerstin , Robinson John A. , Ghasparian Arin 
Published: June 2021

AbstractRespiratory syncytial virus (RSV) can cause severe respiratory disease in humans, particularly in infants and the elderly. However, attempts to develop a safe and effective vaccine have so far been unsuccessful. Atomic-level structures of epitopes targeted by RSV-neutralizing antibodies are now known, including that bound by Motavizumab and its clinically used progenitor Palivizumab. We developed a chemically defined approach to RSV vaccine design, that allows control of both immunogenicity and safety features of the vaccine. Structure-guided antigen design and a synthetic nanoparticle delivery platform led to a vaccine candidate that elicits high titers of palivizumab-like, epitope-specific neutralizing antibodies. The vaccine protects preclinical animal models from RSV infection and lung pathology typical of vaccine-derived disease enhancement. The results suggest that the development of a safe and effective synthetic epitope-specific RSV vaccine may be feasible by combining this conformationally stabilized peptide and synthetic nanoparticle delivery system.
Understanding LRRK2 kinase activity in preclinical models and human subjects through quantitative analysis of LRRK2 and pT73 Rab10
Authors: Wang Xiang , Negrou Elvira , Maloney Michael T. , Bondar Vitaliy V. , Andrews Shan V. , Montalban Manuel , Llapashtica Ceyda , Maciuca Romeo , Nguyen Hoang , Solanoy Hilda , Arguello Annie , Przybyla Laralynne , Moerke Nathan J. , Huntwork-Rodriguez Sarah , Henry Anastasia G. 
Published: June 2021

AbstractVariants in the leucine-rich repeat kinase 2 (LRRK2) gene are associated with increased risk for familial and sporadic Parkinson’s disease (PD). Pathogenic variants in LRRK2, including the common variant G2019S, result in increased LRRK2 kinase activity, supporting the therapeutic potential of LRRK2 kinase inhibitors for PD. To better understand the role of LRRK2 in disease and to support the clinical development of LRRK2 inhibitors, quantitative and high-throughput assays to measure LRRK2 levels and activity are needed. We developed and applied such assays to measure the levels of LRRK2 as well as the phosphorylation of LRRK2 itself or one of its substrates, Rab10 (pT73 Rab10). We observed increased LRRK2 activity in various cellular models of disease, including iPSC-derived microglia, as well as in human subjects carrying the disease-linked variant LRRK2 G2019S. Capitalizing on the high-throughput and sensitive nature of these assays, we detected a significant reduction in LRRK2 activity in subjects carrying missense variants in LRRK2 associated with reduced disease risk. Finally, we optimized these assays to enable analysis of LRRK2 activity following inhibition in human peripheral blood mononuclear cells (PBMCs) and whole blood, demonstrating their potential utility as biomarkers to assess changes in LRRK2 expression and activity in the clinic.
Blood based hybrid nanofluid flow together with electromagnetic field and couple stresses
Authors: Saeed Anwar , Alsubie Abdelaziz , Kumam Poom , Nasir Saleem , Gul Taza , Kumam Wiyada 
Published: June 2021

AbstractIn this investigation, heat transportation together with irreversibility analysis for the flow of couple stress hybrid nanofluid past over a stretching surface is considered. The innovative characteristics and aims of this work are to note that the transportation heat couple stress model involves EMHD, viscous dissipation, Joule heating, and heat absorption, and omission. The hybrid nanofluid is prepared due to the suspension of the solid nanoparticles of the SWCNTs and MWCNTs in pure human blood. This mathematical model is an appropriate model for biological advantages including testing of human blood for drug deliveries to various parts of the human body. Particularly, the Prandtl number used for the blood is 21 and very large as compared to the other base fluids. Necessary modifications are used to translate the defining partial differential equations and boundary conditions into a layout that can be computed. To obtain mathematical approximations for the resulting scheme of nonlinear differential equations, the innovative homotopy analysis method (HAM) is used. The explanation for velocity, energy, and entropy are exposed and the flow against various influential factors ($$E,\;M,\;k,\;Q,\;S\;{\text{and}}\;Ec$$

E
,

M
,

k
,

Q
,

S

and

E
c

) is discussed graphically. The numerical values are calculated and summarized for dimensionless $$C_{{fx}} \;{\text{and}}\;Nu_{x} .$$

C

fx

and

N

u
x

.

In addition, the current study is compared for various values of $$\Pr$$
Pr
to that published literature and an impressive agreement in terms of finding is reported. It has also been noticed that the $$M$$
M
and $$E$$
E
factors retard the hybrid nanofluid flow, while the temperature of fluid becomes upsurges by the rise in these factors. 11.95% enhancement in the heat transfer rate has been attained using the hybrid nanofluids.
Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice
Authors: Tengeler Anouk C. , Emmerzaal Tim L. , Geenen Bram , Verweij Vivienne , van Bodegom Miranda , Morava Eva , Kiliaan Amanda J. , Kozicz Tamas 
Published: June 2021

AbstractExposure to antibiotic treatment has been associated with increased vulnerability to various psychiatric disorders. However, a research gap exists in understanding how adolescent antibiotic therapy affects behavior and cognition. Many antibiotics that target bacterial translation may also affect mitochondrial translation resulting in impaired mitochondrial function. The brain is one of the most metabolically active organs, and hence is the most vulnerable to impaired mitochondrial function. We hypothesized that exposure to antibiotics during early adolescence would directly affect brain mitochondrial function, and result in altered behavior and cognition. We administered amoxicillin, chloramphenicol, or gentamicin in the drinking water to young adolescent male wild-type mice. Next, we assayed mitochondrial oxidative phosphorylation complex activities in the cerebral cortex, performed behavioral screening and targeted mass spectrometry-based acylcarnitine profiling in the cerebral cortex. We found that mice exposed to chloramphenicol showed increased repetitive and compulsive-like behavior in the marble burying test, an accurate and sensitive assay of anxiety, concomitant with decreased mitochondrial complex IV activity. Our results suggest that only adolescent chloramphenicol exposure leads to impaired brain mitochondrial complex IV function, and could therefore be a candidate driver event for increased anxiety-like and repetitive, compulsive-like behaviors.
Effects of climate variation on bird escape distances modulate community responses to global change
Authors: Díaz M. , Grim T. , Markó G. , Morelli F. , Ibáñez-Alamo J. D. , Jokimäki J. , Kaisanlahti-Jokimäki M.-L. , Tätte K. , Tryjanowski P. , Møller A. P. 
Published: June 2021

AbstractClimate and land use are rapidly changing environmental conditions. Behavioral responses to such global perturbations can be used to incorporate interspecific interactions into predictive models of population responses to global change. Flight initiation distance (FID) reflects antipredator behaviour defined as the distance at which an individual takes flight when approached by a human, under standardized conditions. This behavioural trait results from a balance between disturbance, predation risk, food availability and physiological needs, and it is related to geographical range and population trends in European birds. Using 32,145 records of flight initiation distances for 229 bird species during 2006–2019 in 24 European localities, we show that FIDs decreased with increasing temperature and precipitation, as expected if foraging success decreased under warm and humid conditions. Trends were further altered by latitude, urbanisation and body mass, as expected if climate effects on FIDs were mediated by food abundance and need, differing according to position in food webs, supporting foraging models. This provides evidence for a role of behavioural responses within food webs on how bird populations and communities are affected by global change.
Reproducibility and agreement between three positions for handgrip assessment
Authors: Vargas-Pinilla Olga-Cecilia , Rodríguez-Grande Eliana-Isabel 
Published: June 2021

AbstractThe protocol established for taking hand grip dynamometry measurements determines that the patient must be in a sitting position. This protocol cannot be applied due to the patient’s conditions in some cases, such as abdominal surgery, musculoskeletal spine or hip injuries. The purpose was to determine the reproducibility and level of agreement between the Handgrip dynamometry in supine position with the elbow flexed or extended, and the one measured in the sitting position, the design was a descriptive cross-sectional study. The population were young apparently healthy between 18 and 30 years of age (N = 201). Handgrip measurement was performed on both upper limbs in a sitting position with a flexed elbow, a supine position with a flexed elbow, and supine position with the elbow extended. Reproducibility was nearly perfect in all positions (ICC 0.95–0.97). Regarding the level of agreement for the comparison between sitting and supine positions with a flexed elbow, an average difference of − 0.406. For supine position with an extended elbow and supine position with a flexed elbow, the average difference was − 1.479. Considering the results, clinicians or researchers can choose any of the positions evaluated herein and obtain reliable results as long as the standardization process is followed.
Neonatal administration of a subanaesthetic dose of JM-1232(−) in mice results in no behavioural deficits in adulthood
Authors: Iwanaga Koji , Satoh Yasushi , Akai Ryosuke , Ishizuka Toshiaki , Kazama Tomiei , Ikeda Takehiko 
Published: June 2021

AbstractIn animal models, neonatal exposure of general anaesthetics significantly increases apoptosis in the brain, resulting in persistent behavioural deficits later in adulthood. Consequently, there is growing concern about the use of general anaesthetics in obstetric and paediatric practice. JM-1232(−) has been developed as a novel intravenous anaesthetic, but the effects of JM-1232(−) on the developing brain are not understood. Here we show that neonatal administration of JM-1232(−) does not lead to detectable behavioural deficits in adulthood, contrarily to other widely-used intravenous anaesthetics. At postnatal day 6 (P6), mice were injected intraperitoneally with a sedative-equivalent dose of JM-1232(−), propofol, or midazolam. Western blot analysis of forebrain extracts using cleaved poly-(adenosine diphosphate-ribose) polymerase antibody showed that JM-1232(−) is accompanied by slight but measurable apoptosis 6 h after administration, but it was relatively small compared to those of propofol and midazolam. Behavioural studies were performed in adulthood, long after the neonatal anaesthesia, to evaluate the long-term effects on cognitive, social, and affective functions. P6 administration to JM-1232(−) was not accompanied by detectable long-term behavioural deficits in adulthood. However, animals receiving propofol or midazolam had impaired social and/or cognitive functions. These data suggest that JM-1232(−) has prospects for use in obstetric and paediatric practice.