bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1)
Authors: Ali Syed Rydwan , Malone Taylor Joseph , Zhang Yalan , Prechova Magdalena , Kaczmarek Leonard Konrad 
Published: December 2019

AbstractThe Slack (KCNT1) gene encodes sodium‐activated potassium channels that are abundantly expressed in the central nervous system. Human mutations alter the function of Slack channels, resulting in epilepsy and intellectual disability. Most of the disease‐causing mutations are located in the extended cytoplasmic C‐terminus of Slack channels and result in increased Slack current. Previous experiments have shown that the C‐terminus of Slack channels binds a number of cytoplasmic signaling proteins. One of these is Phactr1, an actin‐binding protein that recruits protein phosphatase 1 (PP1) to certain phosphoprotein substrates. Using co‐immunoprecipitation, we found that Phactr1 is required to link the channels to actin. Using patch clamp recordings, we found that co‐expression of Phactr1 with wild‐type Slack channels reduces the current amplitude but has no effect on Slack channels in which a conserved PKC phosphorylation site (S407) that regulates the current amplitude has been mutated. Furthermore, a Phactr1 mutant that disrupts the binding of PP1 but not that of actin fails to alter Slack currents. Our data suggest that Phactr1 regulates the Slack by linking PP1 to the channel. Targeting Slack‐Phactr1 interactions may therefore be helpful in developing the novel therapies for brain disorders associated with the malfunction of Slack channels.
Clinical and Radiographic Outcomes of Modified Unilateral Open-door Laminoplasty with Posterior Muscle-Ligament Complex Preservation for Cervical Spondylotic Myelopathy
Authors: Chen Chao , Yang Cao , Yang Shuhua , Gao Yong , Zhang Yukun , Wu Xinghuo , Hua Wenbin , Shao Zengwu 
Published: December 2019

Mini
The surgical results of modified and traditional open-door laminoplasties were retrospectively compared. There were no differences in neurological outcomes and postoperative complications. However, compared with traditional laminoplasty, modified laminoplasty was associated with better maintenance of cervical curvature and ROM, as well as a lower incidence of postoperative axial symptoms.

Study Design.
A retrospective comparative study.

Objective.
The aim of this study was to evaluate the efficacy of modified unilateral open-door laminoplasty with posterior muscle-ligament complex preservation in treating cervical spondylotic myelopathy (CSM).

Summary of Background Data.
The prevalence of axial symptoms after open-door laminoplasty ranges from 5% to 86%. Current modified laminoplasty techniques cannot satisfactorily reduce postoperative axial symptoms.

Methods.
From June 2014 to July 2016, 36 patients with CSM underwent modified laminoplasty with posterior muscle-ligament complex preservation (modified group) and 27 patients underwent traditional laminoplasty (control group). The demographics, operation duration, blood loss volume, cervical curvature, cervical curvature index (CCI), range of motion (ROM), cervical posterior muscle volume on magnetic resonance imaging (MRI), axial symptoms, visual analog scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and complications were recorded and analyzed before operation, after operation, and at the final follow-up.

Results.
Cervical flexion curvature, cervical curvature, ROM, and CCI were better in the modified group than in controls at the final follow-up (P < 0.01). Postoperative VAS and NDI scores were significantly reduced in the modified group compared with controls (1.15 ± 0.76 vs. 2.63 ± 1.06, 5.67 ± 2.57 vs. 8.89 ± 5.37, respectively) (P < 0.01). Posterior muscle volume at the hinge side in the modified group was not different at final follow-up relative to that before the operation, whereas it was reduced in controls (P < 0.01). Finally, the incidence of axial symptoms was significantly lower in the modified group than in controls (6% vs. 22%) (P = 0.03).

Conclusion.
Modified unilateral open-door laminoplasty with posterior muscle-ligament complex preservation is effective for treating CSM with good recovery of neurological functions and satisfactory maintenance of cervical curvature and ROM. Furthermore, it reduces the incidence of postoperative axial symptoms compared with conventional open-door laminoplasty.

Level of Evidence: 3
Comparison of Food Cue–Evoked and Resting-State Functional Connectivity in Obesity
Authors: Donofry Shannon D. , Jakicic John M. , Rogers Renee J. , Watt Jennifer C. , Roecklein Kathryn A. , Erickson Kirk I. 
Published: December 2019

ABSTRACT

Objective
Obesity is associated with differences in task-evoked and resting-state functional brain connectivity (FC). However, no studies have compared obesity-related differences in FC evoked by high-calorie food cues from that observed at rest. Such a comparison could improve our understanding of the neural mechanisms of reward valuation and decision making in the context of obesity.

Methods
The sample included 122 adults (78% female; mean age = 44.43 [8.67] years) with body mass index (BMI) in the overweight or obese range (mean = 31.28 [3.92] kg/m2). Participants completed a functional magnetic resonance imaging scan that included a resting period followed by a visual food cue task. Whole-brain FC analyses examined seed-to-voxel signal covariation during the presentation of high-calorie food and at rest using seeds located in the left and right orbitofrontal cortex, left hippocampus, and left dorsomedial prefrontal cortex.

Results
For all seeds examined, BMI was associated with stronger FC during the presentation of high-calorie food, but weaker FC at rest. Regions exhibiting BMI-related modulation of signal coherence in the presence of palatable food cues were largely located within the default mode network (z range = 2.34–4.91), whereas regions exhibiting BMI-related modulation of signal coherence at rest were located within the frontostriatal and default mode networks (z range = 3.05–4.11). All FC results exceeded a voxelwise threshold of p < .01 and cluster-defining familywise error threshold of p < .05.

Conclusions
These dissociable patterns of FC may suggest separate neural mechanisms contributing to variation in distinct cognitive, psychological, or behavioral domains that may be related to individual differences in risk for obesity.
Response nonlinearities in networks of spiking neurons
Authors: Sanzeni Alessandro , Histed Mark H. , Brunel Nicolas 
Published: December 2019

ABSTRACTCombining information from multiple sources is a fundamental operation performed by networks of neurons in the brain, whose general principles are still largely unknown. Experimental evidence suggests that combination of inputs in cortex relies on nonlinear summation. Such nonlinearities are thought to be fundamental to perform complex computations. However, these non-linearities contradict the balanced-state model, one of the most popular models of cortical dynamics, which predicts networks have a linear response. This linearity is obtained in the limit of very large recurrent coupling strength. We investigate the stationary response of networks of spiking neurons as a function of coupling strength. We show that, while a linear transfer function emerges at strong coupling, nonlinearities are prominent at finite coupling, both at response onset and close to saturation. We derive a general framework to classify nonlinear responses in these networks and discuss which of them can be captured by rate models. This framework could help to understand the observed diversity of non-linearities observed in cortical networks.AUTHOR SUMMARYModels of cortical networks are often studied in the strong coupling limit, where the so-called balanced state emerges. In this strong coupling limit, networks exhibit without fine tuning, a number of ubiquitous properties of cortex, such as the irregular nature of neuronal firing. However, it fails to account for nonlinear summation of inputs, since the strong coupling limit leads to a linear network transfer function. We show that, in networks of spiking neurons, nonlinearities at response-onset and saturation emerge at finite coupling. Critically, for realistic parameter values, both types of nonlinearities are observed at experimentally observed rates. Thus, we propose that these models could explain experimentally observed nonlinearities.
Removal of Scanner Effects in Covariance Improves Multivariate Pattern Analysis in Neuroimaging Data
Authors: Chen Andrew A. , Beer Joanne C. , Tustison Nicholas J. , Cook Philip A. , Shinohara Russell T. , Shou Haochang ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2019

AbstractTo acquire larger samples for answering complex questions in neuroscience, researchers have increasingly turned to multi-site neuroimaging studies. However, these studies are hindered by differences in images acquired across multiple scanners. These effects have been shown to bias comparison between scanners, mask biologically meaningful associations, and even introduce spurious associations. To address this, the field has focused on harmonizing data by removing scanner-related effects in the mean and variance of measurements. Contemporaneously with the increase in popularity of multi-center imaging, the use of multivariate pattern analysis (MVPA) has also become commonplace. These approaches have been shown to provide improved sensitivity, specificity, and power due to their modeling the joint relationship across measurements in the brain. In this work, we demonstrate that methods for removing scanner effects in mean and variance may not be sufficient for MVPA. This stems from the fact that such methods fail to address how correlations between measurements can vary across scanners. Data from the Alzheimer’s Disease Neuroimaging Initiative is used to show that considerable differences in covariance exist across scanners and that popular harmonization techniques do not address this issue. We also propose a novel methodology that harmonizes covariance of multivariate image measurements across scanners and demonstrate its improved performance in data harmonization.
Pseudomonas aeruginosa is capable of natural transformation in biofilms
Authors: Nolan Laura M. , Turnbull Lynne , Katrib Marilyn , Osvath Sarah R. , Losa Davide , Lazenby James J. , Whitchurch Cynthia B. 
Published: December 2019

AbstractNatural transformation is a mechanism that enables competent bacteria to acquire naked, exogenous DNA from the environment. It is a key process that facilitates the dissemination of antibiotic resistance and virulence determinants throughout bacterial populations. Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that produces large quantities of extracellular DNA (eDNA) that is required for biofilm formation. P. aeruginosa has a remarkable level of genome plasticity and diversity that suggests a high degree of horizontal gene transfer and recombination but is thought to be incapable of natural transformation. Here we show that P. aeruginosa possesses homologs of all proteins known to be involved in natural transformation in other bacterial species. We found that P. aeruginosa in biofilms is competent for natural transformation of both genomic and plasmid DNA. Furthermore, we demonstrate that type IV pili (T4P) facilitate but are not absolutely essential for natural transformation in P. aeruginosa.
Digital polymerase chain reaction in an array of microfluidic printed droplets
Authors: Men Yongfan , Li Jiannan , Ao Tingting , Li Zhihao , Wu Bizhu , Li Wen , Ding Yi , Tseng Kuo-Hao , Tan Wen , Li Baoqing , Chen Yan , Pan Tingrui 
Published: December 2019

AbstractDigital polymerase chain reaction (PCR) is a fast-developed technology, which makes it possible to provide absolute quantitative results. However, this technology has not been widely used in research field or clinical diagnostics. Although digital PCR has been born for two decades, the products on this subject still suffer from either high cost or cumbersome user experience, hence very few labs have the willingness or budget to routinely use such product; On the other hand, the unique sensitivity of dPCR over traditional qPCR shows great potential applications. Here, a cost-effective digital PCR method based on a microfluidic printing system was introduced, trying to overcome those shortcomings. The microfluidic droplet printing technology was utilized in this study to directly generate droplet array containing PCR reaction solution onto the simple glass substrate for the subsequent PCR and imaging, which could be done with any regular flat-panel PCR machine and microscope. The method introduces a new perspective in droplet-based digital PCR in that the droplets generated with this method aligns well in an array without touch with each other, therefore the regular glass and oil could be used without any special surfactant. With simple analysis, the data generated with this method showed reliable quality, which followed the Poisson distribution trend. Compared with other expensive digital PCR methods, this system is more affordable and simpler to integrate, especially for those biological or medical labs which are in need for the digital PCR options but short in budget. Therefore, this method is believed to have the great potential in the future market application.
Comprehensive analysis of lncRNAs reveals candidate prognostic biomarkers in multiple cancer types
Authors: Isaev Keren , Jiang Lingyan , Lee Christian A. , Tsai Ricky , Coutinho Fiona , Dirks Peter B. , Schramek Daniel , Reimand Jüri 
Published: December 2019

ABSTRACTLong non-coding RNAs (lncRNAs) are increasingly recognized as functional units in cancer pathways and powerful molecular biomarkers, however most lncRNAs remain uncharacterized. Here we performed a systematic discovery of prognostic lncRNAs in 9,326 patient tumors of 29 types using a proportional-hazards elastic net machine-learning framework. lncRNAs showed highly tissue-specific transcript abundance patterns. We identified 179 prognostic lncRNAs whose abundance correlated with patient risk and improved the performance of common clinical variables and molecular tumor subtypes. Pathway analysis revealed a large diversity of the high-risk tumors stratified by lncRNAs and suggested their functional associations. In lower-grade gliomas, discrete activation of HOXA10-AS indicated poor patient prognosis, neurodevelopmental pathway activation and a transcriptomic similarity to glioblastomas. HOXA10-AS knockdown in patient-derived glioblastoma cells caused decreased cell proliferation and deregulation of glioma driver genes and proliferation pathways. Our study underlines the pan-cancer potential of the non-coding transcriptome for developing molecular biomarkers and innovative therapeutic strategies.
Performance Monitoring for Sensorimotor Confidence: A Visuomotor Tracking Study
Authors: Locke Shannon M. , Mamassian Pascal , Landy Michael S. 
Published: December 2019

AbstractTo best interact with the external world, humans are often required to consider the quality of their actions. Sometimes the environment furnishes rewards or punishments to signal action efficacy. However, when such feedback is absent or only partial, we must rely on internally generated signals to evaluate our performance (i.e., metacognition). Yet, very little is known about how humans form such judgements of sensorimotor confidence. Do they monitor their performance? Or do they rely on cues to sensorimotor uncertainty to infer how likely it is they performed well? We investigated motor metacognition in two visuomotor tracking experiments, where participants followed an unpredictably moving dot cloud with a mouse cursor as it followed a random trajectory. Their goal was to infer the underlying target generating the dots, track it for several seconds, and then report their confidence in their tracking as better or worse than their average. In Experiment 1, we manipulated task difficulty with two methods: varying the size of the dot cloud and varying the stability of the target’s velocity. In Experiment 2, the stimulus statistics were fixed and duration of the stimulus presentation was varied. We found similar levels of metacognitive sensitivity in all experiments, with the temporal analysis revealing a recency effect, where error later in the trial had a greater influence on the sensorimotor confidence. In sum, these results indicate humans predominantly monitor their tracking performance, albeit inefficiently, to judge sensorimotor confidence.HighlightsParticipants consciously reflected on their tracking performance with some accuracySensorimotor confidence was influenced by recent errorsExpectations of task difficulty did not play a large role in sensorimotor confidenceMetacognitive sensitivity of binary confidence judgements on continuous performance can be quantified with standard non-parametric techniques
Comparative Analysis of In Vitro Responses and Regeneration Between Diverse Bioenergy Sorghum Genotypes
Authors: Flinn Barry S. , Dale Savanah , Disharoon Andrew , Kresovich Stephen 
Published: December 2019

AbstractSorghum has been considered a recalcitrant plant in vitro, and suffers from a lack of regeneration protocols that function broadly and efficiently across a range of genotypes. This study was initiated to identify differential genotype-in vitro protocol responses across a range of bioenergy sorghum bioenergy parental lines, in order to characterize response profiles for use in future genetic studies. Seven bioenergy sorghum genotypes were compared, along with the common grain sorghum genotype Tx430, for their in vitro regeneration responses using two different in vitro protocols, LG and WU. All genotypes displayed some level of response during in vitro culture with both protocols. Distinct genotype-protocol responses were observed, with the WU protocol significantly better for plantlet regeneration. All bioenergy genotypes, with the exception of Chinese Amber, performed as well, if not better than Tx430, with Rio and PI329311 the top regenerating lines. Genotypes displayed protocol-dependent, differential phenolic exudation responses, as indicated by medium browning. During the callus induction phase, genotypes prone to medium browning exhibited a response on WU medium which was either equal or greater than on LG medium, with Pink Kafir and PI329311 the most prone to medium browning. Genotype- and protocol-dependent albino plantlet regeneration was also noted, with three of the bioenergy genotypes showing albino plantlet regeneration. Grassl, Rio and Pink Kafir were susceptible to albino plantlet regeneration, with the response strongly associated with the WU protocol. Pink Kafir displayed the highest albino formation, with close to 25% of regenerating explants forming albino plantlets.
Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts
Authors: Woo Xing Yi , Giordano Jessica , Srivastava Anuj , Zhao Zi-Ming , Lloyd Michael W. , de Bruijn Roebi , Suh Yun-Suhk , Patidar Rajesh , Chen Li , Scherer Sandra , Bailey Matthew , Yang Chieh-Hsiang , Cortes-Sanchez Emilio , Xi Yuanxin , Wang Jing , Wickramasinghe Jayamanna , Kossenkov Andrew V. , Rebecca Vito , Sun Hua , Mashl R. Jay , Davies Sherri , Jeon Ryan , Frech Christian , Randjelovic Jelena , Rosains Jacqueline , Galimi Francesco , Bertotti Andrea , Lafferty Adam , O’Farrell Alice C. , Modave Elodie , Lambrechts Diether , ter Brugge Petra , Serra Violeta , Marangoni Elisabetta , Botty Rania El , Kim Hyunsoo , Kim Jong-Il , Yang Han-Kwang , Lee Charles , Dean Dennis A. , Davis-Dusenbery Brandi , Evrard Yvonne A. , Doroshow James H. , Welm Alana L. , Welm Bryan E. , Lewis Michael T. , Fang Bingliang , Roth Jack A. , Meric-Bernstam Funda , Herlyn Meenhard , Davies Michael , Ding Li , Li Shunqiang , Govindan Ramaswamy , Isella Claudio , Moscow Jeffrey A. , Trusolino Livio , Byrne Annette T. , Jonkers Jos , Bult Carol J. , Medico Enzo , Chuang Jeffrey H. ,   PDXNET consortium,   EurOPDX consortium
Published: December 2019

ABSTRACTPatient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, impacting the accuracy of PDX modeling of human cancer. Here we exhaustively analyze copy number alterations (CNAs) in 1451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multi-region samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.
Control of brown adipose tissue adaptation to nutrient stress by the activin receptor ALK7
Authors: Marmol-Carrasco Patricia , Ibáñez Carlos F. 
Published: December 2019

AbstractAdaptation to nutrient availability is crucial for survival. Upon nutritional stress, such as during prolonged fasting or cold exposure, organisms need to balance the feeding of tissues and the maintenance of body temperature. The mechanisms that regulate the adaptation of brown adipose tissue (BAT), a key organ for non-shivering thermogenesis, to variations in nutritional state are not known. Here we report that specific deletion of the activin receptor ALK7 in BAT resulted in fasting-induced hypothermia due to exaggerated catabolic activity in brown adipocytes. After overnight fasting, BAT lacking ALK7 showed increased expression of genes responsive to nutrient stress, including the upstream regulator KLF15, aminoacid catabolizing enzymes, notably proline dehydrogenase (POX), and adipose triglyceride lipase (ATGL), as well as markedly reduced lipid droplet size. In agreement with this, ligand stimulation of ALK7 suppressed POX and KLF15 expression in both mouse and human brown adipocytes. Treatment of mutant mice with the glucocorticoid receptor (GR) antagonist RU486 restored KLF15 and POX expression levels in mutant BAT, suggesting that loss of BAT ALK7 results in excessive activation of glucocorticoid signaling upon fasting. These results reveal a novel signaling pathway downstream of ALK7 which regulates the adaptation of BAT to nutrient availability by limiting nutrient stress-induced overactivation of catabolic responses in brown adipocytes.
Genetic aberrations in chromatin factors are pervasive, mutually exclusive, associated with a high mutational burden and improved response to checkpoint immunotherapy in cancer
Authors: Markovska Martina , Rosalia Rodney , Stajkovska Aleksandra , Mehandziska Sanja , Janevska Marija , Kungulovski Ivan , Mitrev Zan , Kungulovski Goran 
Published: December 2019

AbstractIn recent years, it has been shown that many of the pervasive genetic defects in cancer occur in chromatin modifiers. Herein, we analyzed the distribution and mutual relationships of genetic aberrations in relevant chromatin modifiers in tens of thousands of publicly available cancer datasets. We observed that in general, they are mutually exclusive, and their prevalence is higher in some types of cancers compared to others. Moreover, we observed a strong association between aberrations in selected chromatin modifiers and tumor mutational burden, leading to an improved response to checkpoint immunotherapy. All in all, this study uncovered interesting relationships between chromatin factors and features of cancer, which warrant follow up functional and clinical studies.