bluuebunny/crossref_metadata_2025_split huggingface dataset:
Counting actin in contractile rings reveals novel contributions of cofilin and type II myosins to fission yeast cytokinesis
Authors: Malla Mamata , Pollard Thomas D. , Chen Qian 
Published: July 2021

AbstractCytokinesis by animals, fungi and amoebas depends on actomyosin contractile rings, which are stabilized by continuous turnover of actin filaments. Remarkably little is known about the amount of polymerized actin in contractile rings, so we used low concentration of GFP-Lifeact to count total polymerized actin molecules in the contractile rings of live fission yeast cells. Contractile rings of wild-type cells accumulated polymerized actin molecules at 4,900/min to a peak number of ∼198,000 followed by a loss of actin at 5,400/min throughout ring constriction. In adf1-M3 mutant cells with cofilin that severs actin filaments poorly, contractile rings accumulated polymerized actin at twice the normal rate and eventually had almost two-fold more actin along with a proportional increase in type II myosins Myo2, Myp2 and formin Cdc12. Although 30% of adf1-M3 mutant cells failed to constrict their rings fully, the rest lost actin from the rings at the wild-type rates. Mutations of type II myosins Myo2 and Myp2 reduced contractile ring actin filaments by half and slowed the rate of actin loss from the rings.
Effects of theta transcranial alternating current stimulation (tACS) on exploration and exploitation during uncertain decision-making
Authors: Wischnewski Miles , Compen Boukje 
Published: July 2021

AbstractExploring ones surroundings may yield unexpected rewards, but is associated with uncertainty and risk. Alternatively, exploitation of certain outcomes is related to low risk, yet potentially better outcomes remain unexamined. As such, risk-taking behavior depends on perceived uncertainty and a trade-off between exploration-exploitation. Previously, it has been suggested that risk-taking may relate to theta activity in the prefrontal cortex. Furthermore, previous studies hinted at a relationship between a right-hemispheric bias in frontal theta asymmetry and risky behavior. In the present double-blind sham-controlled within-subject study, we applied bifrontal transcranial alternating current stimulation (tACS) at the theta frequency (5 Hz) on eighteen healthy volunteers during a gambling task. Two tACS montages with either left-right or posterior-anterior current flow were employed at an intensity of 1 mA. Results showed that, compared to sham, theta tACS increased perceived uncertainty irrespective of current flow direction. Despite this observation, no direct effect of tACS on exploration behavior and general risk-taking was observed. Furthermore, frontal theta asymmetry was more right-hemispherically biased after posterior-anterior tACS, compared to sham. Finally, we used electric field simulation to identify which regions were targeted by the tACS montages as an overlap in regions may explain why the two montages resulted in comparable outcomes. Our findings provide a first step towards understanding the relationship between frontal theta oscillations and different features of risk-taking.Highlights–Risk taking is related to uncertainty, exploration and exploitation–Frontal theta tACS was applied to modulate aspects of risk taking–tACS did increase perceived uncertainty, but not exploration behavior–tACS induced a right hemispheric shift in frontal theta asymmetry
The Alzheimer’s gene SORL1 is a regulator of endosomal traffic and recycling in human neurons
Authors: Mishra Swati , Knupp Allison , Szabo Marcell P. , Williams Charles A. , Kinoshita Chizuru , Hailey Dale W. , Wang Yuliang , Young Jessica E. 
Published: July 2021

ABSTRACTBackgroundLoss of the Sortilin-related receptor 1 (SORL1) gene seems to act as a causal event for Alzheimer’s disease (AD). Recent studies have established that loss of SORL1, as well as mutations in autosomal dominant AD genes APP and PSEN1/2, pathogenically converge by swelling early endosomes, AD’s cytopathological hallmark. Acting together with the retromer trafficking complex, SORL1 has been shown to regulate the recycling of the amyloid precursor protein (APP) out of the endosome, contributing to endosomal swelling and to APP misprocessing. We hypothesized that SORL1 plays a broader role in neuronal endosomal recycling and used human induced pluripotent stem cell derived neurons (hiPSC-Ns) to test this hypothesis. We examined endosomal recycling of three transmembrane proteins linked to AD pathophysiology: APP, the BDNF receptor Tropomyosin-related kinase B (TRKB), and the glutamate receptor subunit AMPA1 (GLUA1).MethodsWe used isogenic hiPSCs engineered to have SORL1 depleted or to have enhanced SORL1 expression. We differentiated neurons from these cell lines and mapped the trafficking of APP, TRKB and GLUA1 within the endosomal network using confocal microscopy. We also performed cell surface recycling and lysosomal degradation assays to assess the functionality of the endosomal network in both SORL1 depleted and overexpressing neurons. Finally, we analyzed alterations in gene expression in SORL1 depleted neurons using RNA-sequencing.ResultsWe find that as with APP, endosomal trafficking of GLUA1 and TRKB is impaired by loss of SORL1. We show that trafficking of all three cargo to late endosomes and lysosomes is affected by manipulating SORL1 expression. We also show that depletion of SORL1 significantly impacts the endosomal recycling pathway for APP and GLUA1 at the level of the recycling endosome and trafficking to the cell surface. This has a functional effect on neuronal activity as shown by multi-electrode array (MEA). Conversely, increased SORL1 expression enhances endosomal recycling for APP and GLUA1. Our unbiased transcriptomic data further support SORL1’s role in endosomal recycling. We observe altered expression networks that regulate cell surface trafficking and neurotrophic signaling in SORL1 depleted neurons.ConclusionCollectively, and together with other recent observations, these findings suggest that SORL1 is a broad regulator of retromer-dependent endosomal recycling in neurons, a conclusion that has both pathogenic and therapeutic implications for Alzheimer’s disease.
Alzheimer’s Disease Classification Accuracy is Improved by MRI Harmonization based on Attention-Guided Generative Adversarial Networks
Authors: Sinha Surabhi , Thomopoulos Sophia I. , Lam Pradeep , Muir Alexandra , Thompson Paul M. 
Published: July 2021

ABSTRACTAlzheimer’s disease (AD) accounts for 60% of dementia cases worldwide; patients with the disease typically suffer from irreversible memory loss and progressive decline in multiple cognitive domains. With brain imaging techniques such as magnetic resonance imaging (MRI), microscopic brain changes are detectable even before abnormal memory loss is detected clinically. Patterns of brain atrophy can be measured using MRI, which gives us an opportunity to facilitate AD detection using image classification techniques. Even so, MRI scanning protocols and scanners differ across studies. The resulting differences in image contrast and signal to noise make it important to train and test classification models on multiple datasets, and to handle shifts in image characteristics across protocols (also known asdomain transferordomain adaptation). Here, we examined whether adversarial domain adaptation can boost the performance of a Convolutional Neural Network (CNN) model designed to classify AD. To test this, we used an Attention-Guided Generative Adversarial Network (GAN) to harmonize images from three publicly available brain MRI datasets - ADNI, AIBL and OASIS - adjusting for scanner-dependent effects. Our AG-GAN optimized a joint objective function that included attention loss, pixel loss, cycle-consistency loss and adversarial loss; the model was trained bidirectionally in an end-to-end fashion. For AD classification, we adapted the popular 2D AlexNet CNN to handle 3D images. Classification based on harmonized MR images significantly outperformed classification based on the three datasets in non-harmonized form, motivating further work on image harmonization using adversarial techniques.
AJILE12: Long-term naturalistic human intracranial neural recordings and pose
Authors: Peterson Steven M. , Singh Satpreet H. , Dichter Benjamin , Scheid Michael , Rao Rajesh P. N. , Brunton Bingni W. 
Published: July 2021

ABSTRACTUnderstanding the neural basis of human movement in naturalistic scenarios is critical for expanding neuroscience research beyond constrained laboratory paradigms. Here, we describe ourAnnotated Joints in Long-term Electrocorticography for 12 human participants(AJILE12) dataset, the largest human neurobehavioral dataset that is publicly available; the dataset was recorded opportunistically during passive clinical epilepsy monitoring. AJILE12 includes synchronized intracranial neural recordings and upper body pose trajectories across 55 semi-continuous days of naturalistic movements, along with relevant metadata, including thousands of wrist movement events and annotated behavioral states. Neural recordings are available at 500 Hz from at least 64 electrodes per participant, for a total of 1280 hours. Pose trajectories at 9 upper-body keypoints were estimated from 118 million video frames. To facilitate data exploration and reuse, we have shared AJILE12 on The DANDI Archive in the Neurodata Without Borders (NWB) data standard and developed a browser-based dashboard.
Determination of best Raman spectroscopy spatial offsets for transcutaneous bone quality assessments in human hands
Authors: Chen Keren , Massie Christine , Awad Hani A. , Berger Andrew J. 
Published: July 2021

AbstractSpatially offset Raman spectroscopy (SORS) is able to detect bone signal transcutaneously and could assist in predicting bone fracture risk. Criteria for optimal source-detector offsets for transcutaneous human measurements, however, are not well-established. Although larger offsets yield a higher percentage of bone signal, the absolute amount of bone signal decreases. Spectral unmixing into bone, adipose, and non-adipose components was employed to quantify changes in bone signal to noise ratio across a range of offsets, and optimal offsets for phalanx and metacarpal measurements were determined. The bone signal to noise ratio was maximized at offsets ranging from 4-6 mm.
Interactive effects of herbivory and the level and fluctuations of nutrient availability on dominance of alien plants in synthetic native communities
Authors: Li Yanjun , Gao Yingzhi , van Kleunen Mark , Liu Yanjie 
Published: July 2021

AbstractNumerous studies have highlighted the role of nutrient availability and fluctuations therein for invasion success of alien plants. Others also highlighted the role of herbivores in invasion success. However, how herbivory and the level and fluctuations in nutrient availability interact in driving alien plant invasion into resident communities remains largely unexplored.We grew eight invasive alien species as target species in pot□mesocosms with five different synthetic native communities in a three-factorial design with two levels of nutrient availability (low vs high), two levels of nutrient fluctuations (constant vs pulsed) and two levels of herbivory (with vs without).The relative biomass production of the alien target plants decreased in response to an increase in nutrient availability, and increased in response to the presence of herbivores. Furthermore, herbivory could interact with changes in nutrient availability and nutrient fluctuations to affect the dominance of the alien target species (a marginally significant interaction; 90% CIs: [0.125, 2.712]).Our multispecies experiment indicates that herbivory could mediate the interactive effect of nutrient enrichment and variability in nutrient supply on invasion of alien plants into native communities. Therefore, we recommend that studies testing the fluctuating resources hypothesis should also consider interactive effect of other trophic levels.
3D Convolutional Neural Networks for Classification of Alzheimer’s and Parkinson’s Disease with T1-Weighted Brain MRI
Authors: Dhinagar Nikhil J. , Thomopoulos Sophia I. , Owens-Walton Conor , Stripelis Dimitris , Ambite Jose Luis , Ver Steeg Greg , Weintraub Daniel , Cook Philip , McMillan Corey , Thompson Paul M. 
Published: July 2021

ABSTRACTParkinson’s disease (PD) and Alzheimer’s disease (AD) are progressive neurodegenerative disorders that affect millions of people worldwide. In this work, we propose a deep learning approach to classify these diseases based on 3D T1-weighted brain MRI. We analyzed several datasets including the Parkinson’s Progression Markers Initiative (PPMI), an independent dataset from the University of Pennsylvania School of Medicine (UPenn), the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and the Open Access Series of Imaging Studies (OASIS) dataset. The UPenn and OASIS datasets were used as independent test sets to evaluate the model performance during inference. We also implemented a random forest classifier as a baseline model by extracting key radiomics features from the same T1-weighted MRI scans. The proposed 3D convolutional neural network (CNN) model was trained from scratch for the classification tasks. For AD classification, the 3D CNN model achieved an ROC-AUC of 0.878 on the ADNI test set and an average ROC-AUC of 0.789 on the OASIS dataset. For PD classification, the proposed 3D CNN model achieved an ROC-AUC of 0.667 on the PPMI test set and an average ROC-AUC of 0.743 on the UPenn dataset. Model performance was largely maintained when using only 25% of the training dataset. The 3D CNN outperformed the random forest classifier for both the PD and AD tasks. The 3D CNN also generalized better on unseen MRI data from different imaging centers. These approaches show promise for screening of PD and AD patients using only T1-weighted brain MRI, which is relatively widely available. This model with additional validation could also be used to help differentiate between challenging cases of AD and PD when they present with similarly subtle motor and non-motor symptoms.
Directed yeast genome evolution by controlled introduction of trans-chromosomic structural variations
Authors: Jia Bin , Jin Jin , Han Ming-Zhe , Li Bing-Zhi , Yuan Ying-Jin 
Published: July 2021

ABSTRACTNaturally occurring structural variations (SVs) are a considerable source of genomic variation and can reshape chromosomes 3D architecture. The synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) system has been proved to generate random SVs to impact phenotypes and thus constitutes powerful drivers of directed genome evolution. However, how to reveal the molecular mechanism insights into the interactions between phenotypes and complex SVs, especially inversions and translocations, has so far remained challenging. In this study, we develop a SV-prone yeast strain by using SCRaMbLE with two synthetic chromosomes, synV and synX. An heterologous biosynthesis pathway allowing a high throughput screen for increased yield of astaxanthin is used as readout and a proof of concept for the application of SV in industry. We report here that complex SVs, including a pericentric inversion and a trans-chromosomes translocation between synV and synX, result in two neochromosomes and a 2.7-fold yield of astaxanthin. We demonstrated that inversion and inversion reshaped chromosomes 3D architecture and led to large reorganization of the genetic information nearby the breakpoint of the SVs along the chromosomes. Specifically, the pericentric inversion increased the expression of STE18 and the trans-chromosomic translocation increased the expression of RPS5 and MCM22, which contributed to higher astaxanthin yield. We also used the model learned from the aforementioned random screen and successfully harnessed the precise introduction of trans-chromosomes translocation and pericentric inversions by rational design. Overall, our work provides an effective tool to not only accelerate the directed genome evolution but also reveal mechanistic insight of complex SVs for altering phenotypes.
Effect of Balloon-Blowing on Dyspnea and Oxygenation in Noncritical Adult Covid19 Patients: A Pilot Study
Authors: Bargahi Mohammad , Soltani Soheil , Rastgoo Nafiseh , Aryanejad Farzane , Nemati Roomina , Ghaebi Mehdi , Bajelan Arezoo , Esmaielzade Sohrab 
Published: July 2021

AbstractDyspnea and decreased O2 saturation are the most common causes of hospitalization in noncritical covid-19 patients. Breathing exercises and chest physiotherapy are used for managing the patients. These treatments are however not well supported by scientific evidence. In a randomized controlled trial, 80 patients were randomly assigned to planned breathing-exercise (n=40) and control groups (n=40). The participants in the intervention group were instructed to blow into a balloon five times a day while lying down. Other therapies were similar in both groups. The severity of dyspnea at rest/after activity and peripheral oxygen saturation (SpO2) with/without O2 therapy were compared between the two groups on the first, second, and third days. The study findings showed no statistically significant difference in SpO2 with/without O2 therapy on the first, second, and third days between the two groups. Although the severity of dyspnea showed no significant difference between the two groups, the mean score of dyspnea at rest (2.72±2.25 vs. 1.6±1.21, p=0.007) and after activity (4.53±2.04 vs. 3.52±1.66, P=0.017) improved in the intervention group on the third day. Balloon-blowing exercise improves dyspnea in noncritical Covid-19 patients, but it does not significantly improve oxygenation.
Multiscale X-ray study of Bacillus subtilis biofilms reveals interlinked structural hierarchy and elemental heterogeneity
Authors: Azulay David N. , Spaeker Oliver , Ghrayeb Mnar , Wilsch-Bräuninger Michaela , Scoppola Ernesto , Burghammer Manfred , Zizak Ivo , Bertinetti Luca , Politi Yael , Chai Liraz 
Published: July 2021

AbstractBiofilms are multicellular microbial communities that encase themselves in an extracellular matrix (ECM) of secreted biopolymers and attach to surfaces and interfaces. Bacterial biofilms are detrimental in hospital and industrial settings, but they can be beneficial in agricultural contexts. An essential property of biofilms that grants them with increased survival relative to planktonic cells is phenotypic heterogeneity; the division of the biofilm population into functionally distinct subgroups of cells. Phenotypic heterogeneity in biofilms can be traced to the cellular level, however, the molecular structures and elemental distribution across whole biofilms as well as possible linkages between them remain unexplored. Mapping X-ray diffraction (XRD) across intact biofilms in time and space, we revealed the dominant structural features in Bacillus subtilis biofilms, stemming from matrix components, spores and water. By simultaneously following the X-ray fluorescence (XRF) signal of biofilms and isolated matrix components, we discovered that the ECM preferentially binds calcium ions over other metal ions, specifically, zinc, manganese and iron. These ions, remaining free to flow below macroscopic wrinkles that act as water channels, eventually accumulate and lead to sporulation. The possible link between ECM properties, regulation of metal ion distribution and sporulation across whole intact biofilms unravels the importance of molecular-level heterogeneity in shaping biofilm physiology and development.Significance StatementBiofilms are multicellular soft microbial communities that are able to colonize synthetic surfaces as well as living organisms. To survive sudden environmental changes and efficiently share their common resources, cells in a biofilm divide into subgroups with distinct functions, leading to phenotypic heterogeneity. Here, by studying intact biofilms by synchrotron X-ray diffraction and fluorescence, we revealed correlations between biofilm macroscopic architectural heterogeneity and the spatio-temporal distribution of extracellular matrix, spores, water and metal ions. Our findings demonstrate that biofilm heterogeneity is not only affected by local genetic expression and cellular differentiation, but also by passive effects resulting from the physicochemical properties of the molecules secreted by the cells, leading to differential distribution of nutrients that propagates through macroscopic length scales.
Thalamic deep brain stimulation as a paradigm to reduce consciousness: implications for cortico-striatal dynamics, absence epilepsy and consciousness studies
Authors: Redinbaugh Michelle J. , Afrasiabi Mohsen , Phillips Jessica M. , Kambi Niranjan A. , Mohanta Sounak , Saalmann Yuri B. 
Published: July 2021

ABSTRACTAnesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but non-specific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in cortico-striato-thalamic (CST) systems, thereby influencing consciousness and related processes. We used multi-microelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes reminiscent of absence epilepsy, here termed absence-like activity (ALA), with decreased behavior and vacant staring coinciding with low-frequency oscillations. DBS modulated ALA likelihood in a frequency-specific manner. ALA events corresponded to decreases in measures of neural complexity (entropy) and integration (Φ*), an index of consciousness, and substantial changes to communication in CST circuits. During ALA, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in cortico-striatal network configurations that dissociated parietal and subcortical structures. Overall, the features of ALA and implicated networks were similar to those of absence epilepsy. As this same multi-microelectrode DBS method – but at different stimulation frequencies – can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of absence epilepsy and other consciousness disorders.SIGNIFICANCEWe use tailored, multi-microelectrode thalamic deep brain stimulation to reversibly decrease consciousness for otherwise healthy, wakeful animals in a stimulation frequency-dependent manner. This represents a bidirectional mechanism for controlling consciousness, as the same method can increase consciousness under certain conditions. Theories of consciousness debate the relative contribution of parietal and frontal lobes, and largely ignore subcortical contributions. In this study, changes in consciousness predominantly involve changes in subcortical and parietal regions, implying that they contribute more to consciousness than frontal regions. Further, decreases in consciousness (indexed by Φ*) coincide with decreased movement, staring, and low-frequency activity in the EEG, similar to absence epilepsy. Thus, the systems-level mechanisms for decreased consciousness in this study have broader clinical implications for absence epilepsy.