bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extraction of common task features in EEG-fMRI data using coupled tensor-tensor decomposition
Authors: Jonmohamadi Yaqub , Muthukumaraswamy Suresh , Chen Joseph , Roberts Jonathan , Crawford Ross , Pandey Ajay 
Published: July 2019

AbstractThe fusion of simultaneously recorded EEG and fMRI data is of great value to neuroscience research due to the complementary properties of the individual modalities. Traditionally, techniques such as PCA and ICA, which rely on strong strong non-physiological assumptions such as orthogonality and statistical independence, have been used for this purpose. Recently, tensor decomposition techniques such as parallel factor analysis have gained more popularity in neuroimaging applications as they are able to inherently contain the multidimensionality of neuroimaging data and achieve uniqueness in decomposition without imposing strong assumptions. Previously, the coupled matrix-tensor decomposition (CMTD) has been applied for the fusion of the EEG and fMRI. Only recently the coupled tensor-tensor decomposition (CTTD) has been proposed. Here for the first time, we propose the use of CTTD of a 4th order EEG tensor (space, time, frequency, and participant) and 3rd order fMRI tensor (space, time, participant), coupled partially in time and participant domains, for the extraction of the task related features in both modalities. We used both the sensor-level and source-level EEG for the coupling. The phase shifted paradigm signals were incorporated as the temporal initializers of the CTTD to extract the task related features. The validation of the approach is demonstrated on simultaneous EEG-fMRI recordings from six participants performing an N-Back memory task. The EEG and fMRI tensors were coupled in 9 components out of which 7 components had a high correlation (more than 0.85) with the task. The result of the fusion recapitulates the well-known attention network as being positively, and the default mode network working negatively time-locked to the memory task.
Endogenous activity modulates stimulus and circuit-specific neural tuning and perception
Authors: Li Yuanning , Ward Michael J. , Richardson R. Mark , G’Sell Max , Ghuman Avniel Singh 
Published: July 2019

AbstractPerception reflects not only input from the sensory periphery, but also the endogenous neural state when sensory inputs enter the brain. Whether endogenous neural states influence perception only through global mechanisms, such as arousal, or can also perception in a neural circuit and stimulus specific manner remains largely unknown. Intracranial recordings from 30 pre-surgical epilepsy patients showed that endogenous activity independently modulated the strength of trial-by-trial neural tuning of different visual category-selective neural circuits. Furthermore, the same aspect of the endogenous activity that influenced tuning in a particular neural circuit also correlated with reaction time only for trials with the category of image that circuit was selective for. These results suggest that endogenous activity may influence neural tuning and perception through circuit-specific predictive coding processes.
Evidence of Chitin in the Ampullae of Lorenzini of Chondrichthyan Fishes
Authors: Phillips Molly , Tang W. Joyce , Robinson Matthew , Daza Daniel Ocampo , Hassan Khan , Leppert Valerie , Hirst Linda S. , Amemiya Chris T. 
Published: July 2019

ABSTRACTChitin is synthesized by a variety of organisms using enzymes called chitin synthases and was recently discovered in a number of aquatic vertebrates. In our ongoing investigations into the presence of vertebrate chitin, we unexpectedly found evidence of the polysaccharide within the electrosensory organs, known as Ampullae of Lorenzini, of diverse chondrichthyan fishes. Experiments with histochemical reagents, chemical analyses, and enzymatic digestions suggested that chitin is a component of the hydrogel filling the structures. Further, in situ hybridization with a sequence from the little skate (Leucoraja erinacea) revealed that chitin synthase expression is localized to cells inside the organs. Collectively, these findings suggest that chondrichthyan fishes endogenously synthesize chitin and beg further investigation into the function of chitin in the electrosensory system.
State-specific gating of salient cues by midbrain dopaminergic input to basal amygdala
Authors: Lutas Andrew , Kucukdereli Hakan , Alturkistani Osama , Carty Crista , Sugden Arthur U. , Fernando Kayla , Diaz Veronica , Flores-Maldonado Vanessa , Andermann Mark L. 
Published: July 2019

AbstractBasal amygdala (BA) neurons guide associative learning via acquisition of responses to stimuli that predict salient appetitive or aversive outcomes. We examined the learning- and state-dependent dynamics of BA neurons and ventral tegmental area dopamine axons that innervate BA (VTADA→BA) using two-photon imaging and photometry in behaving mice. BA neurons did not respond to arbitrary visual stimuli, but acquired responses to stimuli that predicted either rewards or punishments. Most VTADA→BA axons were activated by both rewards and punishments, and acquired responses to cues predicting these outcomes during learning. Responses to cues predicting food rewards in VTADA→BA axons and BA neurons in hungry mice were strongly attenuated following satiation, while responses to cues predicting unavoidable punishments persisted or increased. Therefore, VTADA→BA axons may provide a reinforcement signal of motivational salience that invigorates adaptive behaviors by promoting learned responses to appetitive or aversive cues in distinct, intermingled sets of BA excitatory neurons.
Comparing Functional Connectivity Matrices: A Geometry-Aware Approach applied to Participant Identification
Authors: Venkatesh Manasij , Jaja Joseph , pessoa Luiz 
Published: July 2019

AbstractUnderstanding the correlation structure associated with multiple brain measurements informs about potential “functional groupings” and network organization. The correlation structure can be conveniently captured in a matrix format that summarizes the relationships among a set of brain measurements involving two regions, for example. Such functional connectivity matrix is an important component of many types of investigation focusing on network-level properties of the brain, including clustering brain states, characterizing dynamic functional states, performing participant identification (so-called “fingerprinting”) understanding how tasks reconfigure brain networks, and inter-subject correlation analysis. In these investigations, some notion of proximity or similarity of functional connectivity matrices is employed, such as their Euclidean distance or Pearson correlation (by correlating the matrix entries). Here, we propose the use of a geodesic distance metric that reflects the underlying non-Euclidean geometry of functional correlation matrices. The approach is evaluated in the context of participant identification (fingerprinting): given a participant’s functional connectivity matrix based on resting-state or task data, how effectively can the participant be identified? Using geodesic distance, identification accuracy was over 95% on resting-state data, and exceeded the Pearson correlation approach by 20%. For whole-cortex regions, accuracy improved on a range of tasks by between 2% and as much as 20%. We also investigated identification using pairs of subnetworks (say, dorsal attention plus default mode), and particular combinations improved accuracy over whole-cortex participant identification by over 10%. The geodesic distance also outperformed Pearson correlation when the former employed a fourth of the data as the latter. Finally, we suggest that low-dimensional distance visualizations based on the geodesic approach help uncover the geometry of task functional connectivity in relation to that during resting-state. We propose that the use of the geodesic distance is an effective way to compare the correlation structure of the brain across a broad range of studies.
A hierarchy of migratory keratinocytes maintains the tympanic membrane
Authors: Frumm Stacey M. , Yu Kevin Shengyang , Chang Joseph , Briscoe Jordan A. , Lee Katharine P. , Byrnes Lauren E. , Sneddon Julie B. , Tward Aaron D. 
Published: July 2019

SummaryAlthough the conductive function of the tympanic membrane (TM) is critical for hearing, it is unknown how the organ maintains cellular homeostasis. Using a combination of single-cell RNA sequencing, lineage tracing, whole-organ explant, and live-cell imaging, we demonstrate that the stem cells of the TM epidermis reside in a distinct location at the superior portion of the TM and, as progeny migrate inferiorly, Pdgfra+ fibroblasts maintain a niche supporting proliferation of committed progenitors, while keratinocytes distal from the niche differentiate. Thus, the TM has a three dimensional differentiation hierarchy of keratinocytes distinct from that at other epidermal sites. The TM represents a physiological context where, in the absence of injury, keratinocytes both transit through a proliferative committed progenitor state and exhibit directional lateral migration. This work forms a foundation for understanding common disorders of the TM and introduces a new model system for the understanding of keratinocyte biology.
NEIL2 plays a critical role in limiting inflammation and preserving genomic integrity in H. pylori-infected gastric epithelial cells
Authors: Sahan Ayse Z , Venkova Tatiana , Sayed Ibrahim M. , Beswick Ellen J , Reyes Victor E. , Pinchuk Irina , Sahoo Debashis , Ghosh Pradipta , Hazra Tapas K , Das Soumita 
Published: July 2019

AbstractThe accumulation of Helicobacter pylori infection-induced oxidative DNA damage in gastric epithelial cells is a risk factor for developing gastric cancer (GC); however, the underlying mechanisms remain poorly understood. Here we report that the suppression of NEIL2, an oxidized base-specific mammalian DNA glycosylase, is one such mechanism via which H. pylori infection may fuel the accumulation of DNA damage during the initiation and progression of GC. Using a combination of cultured cell lines and primary cells, we show that expression of NEIL2 is significantly down-regulated after H. pylori infection; such down-regulation was also seen in human gastric biopsies. The H. pylori infection-induced down-regulation of NEIL2 is specific, as Campylobacter jejuni has no such effect. Using gastric organoids isolated from the murine stomach in co-culture studies with live bacteria mimicking the infected stomach lining, we found that H. pylori infection was associated with IL-8 production; this response was more pronounced in Neil2 knockout (KO) mouse cells compared to wild type (WT) cells, suggesting that NEIL2 suppresses inflammation under physiological conditions. Interestingly, DNA damage was significantly higher in Neil2 KO mice compared to WT mice. H. pylori-infected Neil2 KO mice showed higher inflammation and more epithelial cell damage. Computational analysis of gene expression profiles of repair genes in gastric specimens showed the reduction of Neil2 level is linked to the GC progression. Taken together, our data suggest that down-regulation of NEIL2 is a plausible mechanism by which H. pylori infection derails DNA damage repair, amplifies the inflammatory response and initiates GCs.
Mechanisms underlying the response of mouse cortical networks to optogenetic manipulation
Authors: Mahrach Alexandre , Chen Guang , Li Nuo , van Vreeswijk Carl , Hansel David 
Published: July 2019

AbstractGABAergic interneurons can be subdivided into three subclasses: parvalbumin positive (PV), somatostatin positive (SOM) and serotonin positive neurons. With principal cells (PCs) they form complex networks. We examine PCs and PV responses in mouse anterior lateral motor cortex (ALM) and barrel cortex (S1) upon PV photostimulationin vivo. In layer 5, the PV response is paradoxical: photoexcitation reduces their activity. This is not the case in ALM layer 2/3. We combine analytical calculations and numerical simulations to investigate how these results constrain the architecture. Two-population models cannot account for the results. Networks with three inhibitory populations and V1-like architecture account for the data in ALM layer 2/3. Our data in layer 5 can be accounted for if SOM neurons receive inputs only from PCs and PV neurons. In both four-population models, the paradoxical effect implies not too strong recurrent excitation. It is not evidence for stabilization by inhibition.
Injury stimulates stem cells to resist radiation-induced apoptosis
Authors: Shiroor Divya A , Bohr Tisha E , Adler Carolyn E 
Published: July 2019

SummaryStem cells are continuously exposed to multiple stresses including radiation and tissue injury. Because stem cells are central drivers of tissue repair and regeneration, it is essential to understand how their behavior is influenced by these stressors. Planarians have an abundant population of stem cells that are rapidly eliminated after radiation exposure via apoptosis. Low doses of radiation eliminate the majority of these stem cells, allowing a few to remain [1]. Here, we combine radiation with injury to define how surviving stem cells respond to tissue damage. We find that injuries induce stem cells to persist, but only if injured within a defined window of time surrounding radiation, and only immediately adjacent to the wound. Stem cells persist for several days without any proliferation. Instead, they are retained near the wound due to suppression of apoptosis, which we quantify in stem cells by combining FACS with Annexin V staining. Tissue injury is known to induce apoptosis in differentiated cells [2], and we hypothesize that these dying cells confer apoptosis resistance onto nearby stem cells. Indeed, pharmacological induction of cell death with cycloheximide is sufficient to prolong survival of radiated stem cells even in the absence of injury. Together, our results suggest a model in which dying cells provide a transient protective signal to nearby stem cells, altering their susceptibility to radiation-induced apoptosis.
Anti-SSTR2 Antibody-Drug Conjugate for Neuroendocrine Cancer Therapy
Authors: Si Yingnan , Kim Seulhee , Guenter Rachael , Ou Jianfa , Lu Yun , Chen Kai , Zhang John , Whitt Jason , Carter Angela M. , Bibb James A. , Jaskula-Sztul Renata , Markert James M. , Zhou Lufang , Chen Herbert , “Margaret” Liu Xiaoguang 
Published: July 2019

AbstractNeuroendocrine (NE) cancers include a diverse spectrum of hormone-secreting neoplasms that arise from the endocrine and nervous systems. Current chemo- and radio- therapies have marginal curative benefits. This study aimed to develop an innovative antibody-drug conjugate (ADC) to effectively treat NE tumors (NETs). We first confirmed that somatostatin receptor 2 (SSTR2) is an ideal surface target by analyzing 38 patient-derived NET tissues, 33 normal organs, and 3 NET cell lines. We then developed a new monoclonal antibody (mAb, IgG1 and kappa) to target two extracellular domains of SSTR2, which showed strong and specific surface binding to NETs. The ADC was constructed by conjugating the anti-SSTR2 mAb and antimitotic monomethyl auristatin E. In vitro evaluations indicated that the ADC can effectively bind, internalize, release payload, and kill NET cells effectively. Finally, the ADC was evaluated in vivo using a NET xenografted mouse model to determine cancer targeting, maximal tolerated dosage, pharmacokinetics, and anti-cancer efficacy. The anti-SSTR2 ADC was able to exclusively target and kill NETs with minimal toxicity and high stability in vivo. This study demonstrates that the anti-SSTR2 mAb-based ADC has high therapeutic values for NET therapy.
Printable microscale interfaces for long-term peripheral nerve mapping and precision control
Authors: Otchy Timothy M. , Michas Christos , Lee Blaire , Gopalan Krithi , Gleick Jeremy , Semu Dawit , Darkwa Louis , Holinski Bradley J. , Chew Daniel J. , White Alice E. , Gardner Timothy J. 
Published: July 2019

ABSTRACTThe nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying advanced peripheral interfacing technologies. Here, we present a microscale implantable device – the nanoclip – for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high-resolution recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation can achieve a high degree of functionally-relevant modulatory specificity within the small scale of the device. These results highlight the potential of new microscale design and fabrication techniques for the realization of viable implantable devices for long-term peripheral interfacing.
Thalamic and extra-thalamic connections of the Globus Pallidus in the human brain: The ultradirect pathway
Authors: Zheng Zhong S. , Monti Martin M. 
Published: July 2019

AbstractA dominant framework for understanding loss and recovery of consciousness, particularly in the context of severe brain injury, focuses on cortico-subcortical recurrent interactions, with a strong emphasis on excitatory thalamofugal projections. Recent work in healthy volunteers and patients, however, suggests a previously unappreciated role for the globus pallidus pars externa in maintaining a state of consciousness – a finding that is consistent with non-human animal work demonstrating the existence of direct (i.e., extrathalamic) pallido-cortical projections as well as their involvement in modulating electrocortical arousal and sleep. Leveraging on the high-quality Human Connectome Project dataset, we report for the first time in humans, in vivo evidence of (direct) pallido-cortical and pallido-thalamic projections, distinguishing between internal and external pallidal regions. Our data confirm, in humans, the existence of an “ultradirect” extra-thalamic pallido-cortical pathway, with the pars externa connecting preferentially, and extensively, to prefrontal cortex and the pars interna primarily connecting to sensorimotor cortical areas. Furthermore, we also report, for the first time in humans, the likely existence of a direct pathway uniting the globus pallidus pars externa and the medio-dorsal areas of thalamus often implicated in maintenance and recovery of consciousness. Consistent with the pallido-cortical connectivity results, the pars interna appeared to predominantly connect with the sensorimotor areas of thalamus. Collectively, these findings demonstrate the existence in humans of an extra-thalamic “ultradirect” pallido-cortical pathway and suggest a central role of the external segment of the globus pallidum in supporting consciousness.
Dendritic speeding of synaptic potentials in an auditory brainstem principal neuron
Authors: Srinivasan Geetha , Dagostin Andre , Leão Richardson N. , Balakrishnan Veeramuthu , Holcomb Paul , Jackson Dakota , Spirou George , von Gersdorff Henrique 
Published: July 2019

AbstractPrincipal cells of the medial nucleus of the trapezoid body (MNTB) in the mammalian auditory brainstem receive most of their strong synaptic inputs directly on the cell soma. However, these neurons also grow extensive dendrites during the first four postnatal weeks. What are the functional roles of these dendrites? We studied the morphology and growth of the dendrites in the mouse MNTB using both electron microscopy and confocal fluorescence imaging from postnatal day 9 (P9; pre-hearing) to P30. The soma of principal cells sprouted 1 to 3 thin dendrites (diameter ~ 1.5 microns) by P21 to P30. Each dendrite bifurcated into 2-3 branches and spanned an overall distance of about 80 to 200 microns. By contrast, at P9-11 the soma had 1 to 2 dendrites that extended for only 25 microns on average. Patch clamp experiments revealed that the growth of dendrites during development correlates with a progressive decrease in the input resistance, whereas acute removal of dendrites during brain slicing leads to higher input resistances. Accordingly, recordings of excitatory postsynaptic potentials (EPSPs) evoked by afferent fiber stimulation show that EPSP decay is faster in P21-24 neurons with intact dendrites than in neurons without dendrites. This dendritic speeding of the EPSP reduces the decay time constant 5-fold, which will impact significantly synaptic current summation and the ability to fire high-frequency spike trains. These data suggest a novel role for dendrites in auditory brainstem neurons: the speeding of EPSPs for faster and more precise output signal transfer.Significance StatementAuditory circuits that compute sound localization express different types of specialized synapses. Some are capable of fast, precise and sustained synaptic transmission. As the paradigm example, principal cells of the MNTB receive a single calyx-type nerve terminal on their soma and this large excitatory synapse produces fast and brief supra-threshold EPSPs that can trigger trains of high frequency spikes. However, these neurons also extend thin and long dendrites with unknown function. We examined the relationship between dendritic morphology, passive electrical properties and EPSP waveform. We found that more mature neurons with intact dendrites have lower input resistances and short EPSP waveforms, ideally suited for conveying precise timing information, whereas immature neurons with shorter dendrites and higher input resistance have longer lasting EPSPs.
An Automated Addressable Microfluidics Device for Minimally Disruptive Manipulation of Cells and Fluids within Living Cultures
Authors: Tong Anh , Pham Quang Long , Shah Vatsal , Naik Akshay , Abatemarco Paul , Voronov Roman 
Published: July 2019

ABSTRACTAccording to the U.S. Department of Health & Human Services, nearly 115,000 people in the U.S needed a lifesaving organ transplant in 2018, while only ∼10% of them have received it. Yet, almost no artificial FDA-approved products are commercially available today – three decades after the inception of tissue engineering. It is hypothesized here that the major bottlenecks restricting its progress stem from lack of access to the inner pore space of the scaffolds. Specifically, the inability to deliver nutrients to, and clear waste from, the center of the scaffolds limits the size of the products that can be cultured. Likewise, the inability to monitor, and control, the cells after seeding them into the scaffold results in nonviable tissue, with an unacceptable product variability. To resolve these bottlenecks, we present a prototype addressable microfluidics device capable of minimally disruptive fluid and cell manipulations within living cultures. As proof-of-concept, we demonstrate its ability to perform additive manufacturing by seeding cells in spatial patterns (including co-culturing multiple cell types); and subtractive manufacturing by removing surface adherent cells via focused flow of trypsin. Additionally, we show that the device can sample fluids and perform cell “biopsies” (which can be subsequently sent for ex-situ analysis), from any location within its Culture Chamber. Finally, the on-chip plumbing is completely automated using external electronics. This opens the possibility to perform long-term computer-driven tissue engineering experiments, where the cell behavior is modulated in response to the minimally disruptive observations (e.g. fluid sampling and cell biopsies) throughout the entire duration of the cultures. It is expected that the proof-of-concept technology will eventually be scaled up to 3D addressable microfluidic scaffolds, capable of overcoming the limitations bottlenecking the transition of tissue engineering technologies to the clinical setting.