bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electromagnetic mapping of the effects of deep brain stimulation and dopaminergic medication on movement-related cortical activity and corticomuscular coherence in Parkinson’s disease
Authors: Sridharan Kousik Sarathy , Højlund Andreas , Johnsen Erik Lisbjerg , Sunde Niels Aagaard , Beniczky Sándor , Østergaard Karen 
Published: June 2019

AbstractBackgroundParkinson’s disease (PD) is a debilitating neurodegenerative disorder. PD can be treated with deep brain stimulation (DBS) when dopaminergic medication is no longer a viable option. Both treatments are effective in improving motor symptoms, however, their underlying mechanisms are not fully elucidated yet.ObjectivesTo study the effects of DBS and dopaminergic medication treatments on cortical processing and corticomuscular drive during movements.MethodsMagnetoencephalography (MEG) was recorded in 10 PD patients and 10 healthy controls, performing phasic hand contractions (hand gripping). Measurements were performed in DBS-treated, untreated and dopaminergic-medicated states; healthy controls received no treatment interventions. Participants performed phasic contractions with their right hand, recorded with electromyography (EMG). Our measures of interest were beta (13-30 Hz) corticomuscular coherence (CMC) and low-gamma (31-45 Hz) power. We used Bayesian statistics on summary values from sensor space data, and we localized the sources of the effects of treatments on beta-CMC and low-gamma power using beamforming.ResultsIn PD patients, DBS led to reduced CMC values, whereas dopaminergic medication increased beta-CMC values (localized to contralateral M1) to even higher levels than the controls. DBS, on the other hand, increased low-gamma power (localized to M1) compared to controls and to other conditions. Yet both treatments had similar beneficial effects on the patients’ motor symptoms evaluated by UPDRS-III.ConclusionDespite comparable improvements from both treatments on motor symptoms, DBS and dopaminergic medication seem to have different effects on motor cortical function. This indicates that the treatments undertake different functional strategies to improve PD symptoms.
Learning Context-aware Structural Representations to Predict Antigen and Antibody Binding Interfaces
Authors: Pittala Srivamshi , Bailey-Kellogg Chris 
Published: June 2019

AbstractUnderstanding how antibodies specifically interact with their antigens can enable better drug and vaccine design, as well as provide insights into natural immunity. Experimental structural characterization can detail the “ground truth” of antibody-antigen interactions, but computational methods are required to efficiently scale to large-scale studies. In order to increase prediction accuracy as well as to provide a means to gain new biological insights into these interactions, we have developed a unified deep learning-based framework to predict binding interfaces on both antibodies and antigens. The framework leverages three key aspects of antibody-antigen interactions in order to learn predictive structural representations: (1) since interfaces are formed from multiple residues in spatial proximity, we employ graph convolutions to aggregate properties across local regions in a protein; (2) since interactions are specific between antibody-antigen pairs, we employ an attention layer to explicitly encode the context of the partner; (3) since more data is available for general protein-protein interactions, we employ transfer learning to leverage this data as a prior for the specific case of antibody-antigen interactions. We show that this single framework achieves state-of-the-art performance at predicting binding interfaces on both antibodies and antigens, and that each of its three aspects drives additional improvement in the performance. We further show that the attention layer not only improves performance, but also provides a biologically interpretable perspective into the mode of interaction.
Walking cadence affects the recruitment of the medial-lateral balance mechanisms
Authors: Fettrow Tyler , Reimann Hendrik , Grenet David , Crenshaw Jeremy , Higginson Jill , Jeka John 
Published: June 2019

AbstractWe have previously identified three balance mechanisms that young healthy adults use to maintain balance while walking. The three mechanisms are: 1) The lateral ankle mechanism, an active modulation of ankle inversion/eversion in stance; 2) The foot placement mechanism, an active shift of the swing foot placement; and 3) The push-off mechanism, an active modulation of the ankle plantarflexion angle during double stance. Here we seek to determine whether there are changes in neural control of balance when walking at different cadences and speeds. Twenty-one healthy young adults walked on a self-paced treadmill while immersed in a 3D virtual reality cave, and periodically received balance perturbations (bipolar galvanic vestibular stimulation) eliciting a perceived fall to the side. Subjects were instructed to match two cadences specified by a metronome, 110bpm (High) and 80bpm (Low), which led to faster and slower gait speeds, respectively. The results indicate that subjects altered the use of the balance mechanisms at different cadences. The lateral ankle mechanism was used more in the Low condition, while the foot placement mechanism was used more in the High condition. There was no difference in the use of the push-off mechanism between cadence conditions. These results suggest that neural control of balance is altered when gait characteristics such as cadence change, suggesting a flexible balance response that is sensitive to the constraints of the gait cycle. We speculate that the use of the balance mechanisms may be a factor resulting in well-known characteristics of gait in populations with compromised balance control, such as slower gait speed in older adults or higher cadence in people with Parkinson’s disease.
Localist neural plasticity identified by mutual information
Authors: Scheler Gabriele , Schumann Martin L , Schumann Johann 
Published: June 2019

AbstractWe present a model of pattern memory and retrieval with novel, technically useful and biologically realistic properties. Specifically, we enter n variations of k pattern classes (n*k patterns) onto a cortex-like balanced inhibitory-excitatory network with heterogeneous neurons, and let the pattern spread within the recurrent network. We show that we can identify high mutual-information (MI) neurons as major information-bearing elements within each pattern representation. We employ a simple one-shot adaptive (learning) process focusing on high MI neurons and inhibition. Such ‘localist plasticity’ has high efficiency, because it requires only few adaptations for each pattern. Specifically, we store k=10 patterns of size s=400 in a 1000/1200 neuron network. We stimulate high MI neurons and in this way recall patterns, such that the whole network represents this pattern. We assess the quality of the representation (a) before learning, when entering the pattern into a naive network, (b) after learning, on the adapted network, and (c) after recall by stimulation. The recalled patterns could be easily recognized by a trained classifier. The recalled pattern ‘unfolds’ over the recurrent network with high similarity to the original input pattern. We discuss the distribution of neuron properties in the network, and find that an initial Gaussian distribution changes into a more heavy-tailed, lognormal distribution during the adaptation process. The remarkable result is that we are able to achieve reliable pattern recall by stimulating only high information neurons. This work provides a biologically-inspired model of cortical memory and may have interesting technical applications.
A rule-based data-informed cellular consensus map of the human mononuclear phagocyte cell space
Authors: Günther Patrick , Cirovic Branko , Baßler Kevin , Händler Kristian , Becker Matthias , Dutertre Charles Antoine , Bigley Venetia , Newell Evan , Collin Matthew , Ginhoux Florent , Schlitzer Andreas , Schultze Joachim L. 
Published: June 2019

AbstractSingle-cell genomic techniques are opening new avenues to understand the basic units of life. Large international efforts, such as those to derive a Human Cell Atlas, are driving progress in this area; here, cellular map generation is key. To expedite the inevitable iterations of these underlying maps, we have developed a rule-based data-informed approach to build next generation cellular consensus maps. Using the human dendritic-cell and monocyte compartment in peripheral blood as an example, we performed computational integration of previous, partially overlapping maps using an approach we termed ‘backmapping’, combined with multi-color flow-cytometry and index sorting-based single-cell RNA-sequencing. Our general strategy can be applied to any atlas generation for humans and other species.Graphical AbstractHighlightsDefining a consensus of the human myeloid cell compartment in peripheral blood3 monocytes subsets, pDC, cDC1, DC2, DC3 and precursor DC make up the compartmentDistinguish myeloid cell compartment from other cell spaces, e.g. the NK cell spaceProviding a generalizable method for building consensus maps for the life sciences
A versatile ES cell-based melanoma mouse modeling platform
Authors: Bok Ilah , Vera Olga , Xu Xiaonan , Jasani Neel , Nakamura Koji , Reff Jordan , Nenci Arianna , Gonzalez Jose G. , Karreth Florian A. 
Published: June 2019

AbstractThe cumbersome and time-consuming process of generating new mouse strains and multi-allelic experimental animals often hinders the use of genetically engineered mouse models (GEMM) in cancer research. Here, we describe the development and validation of an embryonic stem cell (ESC)-GEMM platform for rapid modeling of melanoma in mice. Our platform incorporates twelve clinically relevant genotypes composed of combinations of four driver alleles (LSL-BrafV600E, LSL-NrasQ61R, PtenFlox, Cdkn2aFlox) and regulatory alleles to spatiotemporally control the perturbation of genes-of-interest. Our ESCs produce high contribution chimeras, which recapitulate the melanoma phenotypes of conventionally bred mice. Using our ESC-GEMM platform to modulate Pten expression in melanocytes in vivo, we highlight the utility and advantages of gene depletion by CRISPR-Cas9, RNAi, or conditional knockout for melanoma modeling. Moreover, we use complementary genetic methods to demonstrate the impact of Pten restoration on the prevention and maintenance of Pten-deficient melanomas. Finally, we show that chimera-derived melanoma cell lines retain regulatory allele competency and are a powerful resource to complement ESC-GEMM chimera experiments in vitro and in syngeneic grafts in vivo. Thus, when combined with sophisticated genetic tools, our ESC-GEMM platform enables rapid, high-throughput, and versatile studies aimed at addressing outstanding questions in melanoma biology.
The cohesin loader NIPBL interacts with pre-ribosomal RNA and treacle to regulate ribosomal RNA synthesis
Authors: Kong Xiangduo , Chen Yen-Yun , Lin Jianhuang , Flowers Ebony , Van Nostrand Eric , Blue Steven M. , Chau Jonathan , Ma Christopher I-Hsing , Mohr Isaiah , Thai Ryan , Yao Chengguo , Ball Alexander R. , Chien Richard , Kawauchi Shimako , Santos Rosaysela , Calof Anne L. , Lander Arthur D. , Shi Yongsheng , Okuwaki Mitsuru , Yeo Gene W. , Yokomori Kyoko 
Published: June 2019

AbstractNIPBL is an essential loader of cohesin to mediate sister chromatid cohesion and chromatin loop organization. NIPBL mutations cause Cornelia de Lange Syndrome. How NIPBL’s genomic localization is specified is not fully understood. We found that NIPBL localizes to the nucleolus in an RNA-dependent manner and binds directly to ribosomal RNA (rRNA). We identified two RNA binding domains in NIPBL in vitro, both of which are required for efficient rRNA binding in vivo. NIPBL binds to ribosomal DNA (rDNA) in an RNA-stimulated manner, recruits PAF1 and promotes pre-rRNA transcription. Stress that inhibits rRNA synthesis displaces NIPBL from the nucleolus and rDNA. Interestingly, treacle, mutated in Treacher Collins syndrome, tightly binds to and recruits NIPBL to the nucleolus, nucleolar organizer regions, and the stress-induced nucleolar cap. The results reveal that a subpopulation of NIPBL is recruited to the nucleolus through its interaction with RNA and treacle and regulates pre-rRNA transcription.
Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1
Authors: Yin Qi , Wang Hongye , Xie Zhenfei , Jin Lifang , Ding Yifu , Li Na , Li Yan , Wang Qiong , Liu Xinyi , Xu Liuqing , Wang Kai , Cheng Yanbo , Chang Boran , Zhong Cuiqing , Yu Qian , Tang Wei , Chen Wanjin , Yang Wenjun , Zhang Fan , Ding Chen , Bao Lan , Zhou Bin , Hu Ping , Li Jinsong 
Published: June 2019

AbstractMultisystem manifestations in myotonic dystrophy type 1 (DM1) may be due to dosage reduction in multiple genes induced by aberrant expansion of CTG repeats in DMPK, including Dmpk and its neighboring genes (Six5 or Dmwd) and downstream Mbnl1. However, the direct evidences are lack. Here, we develop a new strategy to generate mice carrying multigene mutations in one step by injection of haploid embryonic stem cells with mutant Dmpk, Six5 and Mbnl1 into oocytes. The triple heterozygous mutant mice exhibit adult-onset DM1 phenotypes. With the additional mutation in Dmwd, quadruple heterozygous mutant mice recapitulate many major manifestations in congenital DM1. Moreover, muscle stem cells in both models display reduced stemness. Our results suggest that the complex symptoms of DM1 result from the reduced gene dosage of multiple genes.
Control of Septoria tritici blotch by winter wheat cultivar mixtures: Meta-analysis of 19 years of cultivar trials
Authors: Kristoffersen Rose , Jørgensen Lise Nistrup , Eriksen Lars Bonde , Nielsen Ghita Cordsen , Kiær Lars Pødenphant 
Published: June 2019

AbstractWheat is the most commonly grown cereal crop in Europe and in major parts the most yield limiting disease is Septoria tritici blotch (STB). Currently, the control of the disease depends on cultivar resistance and significant input of fungicides. The impact of using mixtures of elite cultivars as an alternative was investigated through a meta-analysis based on trial data from the Danish national cultivar testing. The cultivar testing includes a four-way cultivar mixture every year and in these trials STB severity and yield have been monitored at multiple locations between 1995 and 2017. Results from 19 years of cultivar testing trials provided a data set for 406 trials from which the effect of mixtures was evaluated. The meta-analysis revealed that cultivar mixtures reduced STB severity with 10.6% and increased yields with 1.4% across all trials. The effects were greatest in untreated trials where STB severity was reduced with 17% and yields increased with 2.4%. The mixtures did not only perform better than the average of their component cultivars grown as pure stand, they also performed better than the average of the four most grown cultivars in a given year. No relationship was found between disease pressure or location and the performance of the mixtures. The mixtures included in the cultivar testing were not designed to control STB and the results are therefore perceived as a baseline to the attainable disease control from mixtures. The use of cultivar mixtures is relevant for low input farming systems, but can also contribute to disease control in intensive farming systems. Cultivar mixtures have the potential to minimise dependency on fungicides as an important element in integrated pest management.
Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion
Authors: Rabieifar Parisa , Zhuang Ting , Costa Tânia D. F. , Zhao Miao , Strömblad Staffan 
Published: June 2019

Abstractp21-activated protein kinases (PAKs) are serine/threonine kinases functioning as downstream effectors of the small GTPases Rac1 and Cdc42. Members of the PAK family are overexpressed in human breast cancer, but their role in mammary gland development is not fully explored. Here we examined the functional role of PAK4 in mammary gland development by creating a mouse model of MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland. The PAK4 conditional knock-out mice were born healthy with no observed developmental deficits. Mammary gland whole-mounts revealed no defects in ductal formation or elongation of the mammary tree through the fat pad. PAK4 gene depletion also did not alter proliferation and invasion of the mammary epithelium in young virgin mice. Moreover, adult mice gave birth to healthy pups with normal body weight upon weaning. This implies that MMTV-Cre induced gene depletion of PAK4 in mice does not impair normal mammary gland development and thereby provides anin vivomodel for examination of the potential function of PAK4 in breast cancer.
Characteristics of University Students Supported by Counseling Services: Analysis of psychological tests and pulse rate variability
Authors: Adachi Yumi , Yoshikawa Hiroaki , Yokoyama Shigeru , Iwasa Kazuo 
Published: June 2019

AbstractObjectiveThe number of students who use counseling services is increasing in universities. We clarified the characteristics of the students who access counseling services using both psychological tests and pulse rate variability (PRV).MethodsWe recruited the participants for this study from the students who had counseling sessions at Kanazawa University (Group S). As a control group, we also recruited students who had no experience in counseling sessions (Group H). We obtained health information from the database of annual health check-ups. Participants received the Wechsler Adult Intelligence Scale (WAIS) III, Autism-Spectrum Quotient (AQ), Sukemune-Hiew (S-H) Resilience Test, and State-Trait Anxiety Inventory-JYZ (STAI). We also studied the SF-12v2 Health Survey. We examined the spectral analyses of pulse rate variability (PRV) by accelerating plethysmography. We performed linear analysis of PRV for LF, HF, and LF/HF as indexes of autonomic nervous function. We also performed non-linear analysis of PRV for the largest Lyapunov exponent (LLE). We examined participants’ blood for autoantibodies against glutamate decarboxylase (GAD) 65.ResultsA total of 105 students participated in this study. Group S had 37 participants (Male: 26, Female: 11) and Group H had 68 participants (Male: 27, Female 41). There were 12 males and two females who had been diagnosed with autism spectrum disorder (ASD) in Group S. Group S had 1) lower Working Memory Index (WMI) despite relatively high Full-Scale IQ, 2) higher AQ scores, 3) lower resilience scores, 4) higher anxiety scores, 5)lower QOL in social health, and 6) shifting of autonomic nervous balance toward higher sympathetic activity. There were only two participants who had the anti-GAD65 antibody in Group S, and one participant had the anti-GAD65 antibody in Group H.ConclusionThe results of our study revealed valuable information about the students who seek mental support in our university. Our results provide information that can be used in interventions for the university students who need counseling services.
Long-term influence of climate and experimental eutrophication regimes on phytoplankton blooms
Authors: Salk Kateri R. , Venkiteswaran Jason J. , Couture Raoul-Marie , Higgins Scott N. , Paterson Michael J. , Schiff Sherry L. 
Published: June 2019

AbstractPhytoplankton blooms respond to multiple drivers, including climate change and nutrient loading. Here we examine a long-term dataset from Lake 227, a site exposed to a fertilization experiment (1969–present). Changes in nitrogen:phosphorus loading ratios (high N:P, low N:P, P-only) did not impact mean annual biomass, but blooms exhibited substantial inter- and intra-annual variability. We used a process-oriented lake model, MyLake, to successfully reproduce lake physics over 48 years and test if a P-limited model structure predicted blooms. The timing and magnitude of blooms was reproduced during the P-only period but not for the high and low N:P periods, perhaps due to N acquisition pathways not currently included in the model. A model scenario with no experimental fertilization confirmed P loading is the major driver of blooms, while a scenario that removed climate-driven temperature trends showed that increased spring temperatures have exacerbated blooms beyond the effects of fertilization alone.Significance StatementHarmful algal blooms and eutrophication are key water quality issues worldwide. Managing algal blooms is often difficult because multiple drivers, such as climate change and nutrient loading, act concurrently and potentially synergistically. Long-term datasets and simulation models allow us to parse the effects of interacting drivers of blooms. The performance of our model depended on the ratio of nitrogen to phosphorus inputs, suggesting that complex biological dynamics control blooms under variable nutrient loads. We found that blooms were dampened under a “no climate change” scenario, suggesting that the interaction of nutrient loading and increased temperature intensifies blooms. Our results highlight successes and gaps in our ability to model blooms, helping to establish future management recommendations.Data Availability StatementData and metadata will be made available in a GitHub repository (https://github.com/biogeochemistry/Lake-227). Upon manuscript acceptance, the repository will be made publicly available and a DOI will be provided. We request that data users contact the Experimental Lakes Area directly, per their data use policy (http://www.iisd.org/ela/wp-content/uploads/2016/04/Data-Terms-And-Conditions.pdf).
Conditional, inducible gene silencing in dopamine neurons reveals a sex-specific role for Rit2 GTPase in acute cocaine response and striatal function
Authors: Sweeney Carolyn G. , Kearney Patrick J. , Fagan Rita R. , Smith Lindsey A. , Bolden Nicholas C. , Zhao-Shea Rubing , Rivera Iris V. , Kolpakova Jenya , Xie Jun , Gao Guangping , Tapper Andrew R. , Martin Gilles E. , Melikian Haley E. 
Published: June 2019

AbstractDopamine (DA) signaling is critical for movement, motivation, and addictive behavior. The neuronal GTPase, Rit2, is enriched in DA neurons (DANs), binds directly to the DA transporter (DAT), and is implicated in several DA-related neuropsychiatric disorders. However, it remains unknown whether Rit2 plays a role in either DAergic signaling and/or DA-dependent behaviors. Here, we leveraged the TET-OFF system to conditionally silence Rit2 in Pitx3IRES2-tTA mouse DANs. Following DAergic Rit2 knockdown (Rit2-KD), mice displayed an anxiolytic phenotype, with no change in baseline locomotion. Further, males exhibited increased acute cocaine sensitivity, whereas DAergic Rit2-KD suppressed acute cocaine sensitivity in females. DAergic Rit2-KD did not affect presynaptic TH and DAT protein levels in females, nor was TH was affected in males; however, DAT was significantly diminished in males. Paradoxically, despite decreased DAT levels in males, striatal DA uptake was enhanced, but was not due to enhanced DAT surface expression in either dorsal or ventral striatum. Finally, patch recordings in nucleus accumbens (NAcc) medium spiny neurons (MSNs) revealed reciprocal changes in spontaneous EPSP (sEPSP) frequency in male and female D1+ and D2+ MSNs following DAergic Rit2-KD. In males, sEPSP frequency was decreased in D1+, but not D2+, MSNs, whereas in females sEPSP frequency decreased in D2+, but not D1+, MSNs. Moreover, DAergic Rit2-KD abolished the ability of cocaine to reduce sEPSP frequency in D1+, but not D2+, male MSNs. Taken together, our studies are among the first to acheive AAV-mediated, conditional and inducible DAergic knockdown in vivo. Importantly, our results provide the first evidence that DAergic Rit2 expression differentially impacts striatal function and DA-dependent behaviors in males and females.