bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Normal Pressure Hydrocephalus by Disease-Specific Patterns of Brain Stiffness and Damping Ratio
Authors: Murphy Matthew C. , Cogswell Petrice M. , Trzasko Joshua D. , Manduca Armando , Senjem Matthew L. , Meyer Fredric B. , Ehman Richard L. , Huston John 
Published: February 2020

ObjectivesThe aim of this study was to perform a whole-brain analysis of alterations in brain mechanical properties due to normal pressure hydrocephalus (NPH).Materials and MethodsMagnetic resonance elastography (MRE) examinations were performed on 85 participants, including 44 cognitively unimpaired controls, 33 with NPH, and 8 who were amyloid-positive with Alzheimer clinical syndrome. A custom neural network inversion was used to estimate stiffness and damping ratio from patches of displacement data, accounting for edges by training the network to estimate the mechanical properties in the presence of missing data. This learned inversion was first compared with a standard analytical approach in simulation experiments and then applied to the in vivo MRE measurements. The effect of NPH on the mechanical properties was then assessed by voxel-wise modeling of the stiffness and damping ratio maps. Finally, a pattern analysis was performed on each individual's mechanical property maps by computing the correlation between each person's maps with the expected NPH effect. These features were used to fit a classifier and assess diagnostic accuracy.ResultsThe voxel-wise analysis of the in vivo mechanical property maps revealed a unique pattern in participants with NPH, including a concentric pattern of stiffening near the dural surface and softening near the ventricles, as well as decreased damping ratio predominantly in superior regions of the white matter (family-wise error correctedP< 0.05 at cluster level). The pattern of viscoelastic changes in each participant predicted NPH status in this cohort, separating participants with NPH from the control and the amyloid-positive with Alzheimer clinical syndrome groups, with areas under the receiver operating characteristic curve of 0.999 and 1, respectively.ConclusionsThis study provides motivation for further development of the neural network inversion framework and demonstrates the potential of MRE as a novel tool to diagnose NPH and provide a window into its pathogenesis.
Long-Term Persistence of IgG Antibodies in SARS-CoV Infected Healthcare Workers
Authors: Guo Xiaoqin , Guo Zhongmin , Duan Chaohui , Chen Zeliang , Wang Guoling , Lu Yi , Li Mengfeng , Lu Jiahai 
Published: February 2020

ABSTRACTBACKGROUNDThe ongoing worldwide outbreak of the 2019-nCoV is markedly similar to the severe acute respiratory syndrome (SARS) outbreak 17 years ago. During the 2002-2003 SARS outbreak, healthcare workers formed a special population of patients. Although virus-specific IgG play important roles in virus neutralization and prevention against future infection, limited information is available regarding the long term persistence of IgG after infection with SARS-like coronavirus.METHODSA long-term prospective cohort study followed 34 SARS-CoV-infected healthcare workers from a hospital with clustered infected cases during the 2002-2003 SARS outbreak in Guangzhou, China, with a 13-year follow-up. Serum samples were collected annually from 2003-2015. Twenty SARS-CoV-infected and 40 non-infected healthcare workers were enrolled in 2015, and their serum samples were collected. All sera were tested for IgG antibodies with ELISA using whole virus and a recombinant nucleocapsid protein of SARS-CoV, as a diagnostic antigen.RESULTSAnti SARS-CoV IgG was found to persist for up to 12 years. IgG titers typically peaked in 2004, declining rapidly from 2004-2006, and then continued to decline at a slower rate. IgG titers in SARS-CoV-infected healthcare workers remained at a significantly high level until 2015. Patients treated with corticosteroids at the time of infection were found to have lower IgG titers than those without.CONCLUSIONSIgG antibodies against SARS-CoV can persist for at least 12 years. The presence of SARS-CoV IgG might provide protection against SARS-CoV and other betacoronavirus. This study provides valuable information regarding humoral immune responses against SARS-CoV and the 2019-nCoV.
Macrophages transfer mitochondria to sensory neurons to resolve inflammatory pain
Authors: van der Vlist Michiel , Raoof Ramin , Willemen Hanneke L.D.M. , Prado Judith , Versteeg Sabine , Gil Christian Martin , Vos Martijn , Lokhorst Roeland E. , Pasterkamp R. Jeroen , Kojima Toshiyuki , Karasuyama Hajime , Khoury-Hanold William , Meyaard Linde , Eijkelkamp Niels 
Published: February 2020

SummaryThe current paradigm is that inflammatory pain passively resolves following the cessation of inflammation. Yet, in a substantial proportion of patients with inflammatory diseases, resolution of inflammation is not sufficient to resolve pain, resulting in chronic pain. Mechanistic insight how inflammatory pain is resolved is lacking. Here we show that macrophages actively control resolution of inflammatory pain remotely from the site of inflammation by transferring mitochondria to sensory neurons. During resolution of inflammatory pain in mice, M2-like macrophages infiltrate the dorsal root ganglia that contain the somata of sensory neurons, concurrent with the recovery of oxidative phosphorylation in sensory neurons. The resolution of pain and the transfer of mitochondria requires expression of CD200 Receptor (CD200R) on macrophages and the non-canonical CD200R-ligand iSec1 on sensory neurons. Our data reveal a novel mechanism for active resolution of inflammatory pain.Graphical Abstract
Towards understanding the structure of the capsid of Banana Bunchy Top Virus
Authors: Sairam Sundaram , Selvarajan Ramasamy , Handanahalli Savithri S , Venkataraman Sangita 
Published: February 2020

AbstractBanana is the major staple food crop for approximately 400 million people. Bunchy Top disease of Banana is one of the most devastating diseases caused by Banana Bunchy Top Virus (BBTV) that results in a significant loss of yield, stunting and bunchy appearance of leaves. While many isolates of BBTV from various regions of India have been characterized by different groups, no structural study exists for this important virus. To pursue structural studies, the pET28a clone of coat protein (CP) gene from BBTV isolate of Hill Banana grown in lower Pulney Hills (Virupakshi) of Tamilnadu was expressed in BL21 (DE3) pLysS. Purification of the CP was done using Ni-NTA affinity chromatography. In vitro capsid assembly studied using sucrose density gradient centrifugation suggested that the CP did not assemble as virus like particle (VLPs) but remained as smaller oligomers. Studies using dynamic light scattering (DLS) indicates that the purified protein is poly-dispersed represented majorly as pentamers. Studies using both homology modelling andab initiostructure determination gave useful insights into the probable fold of the CP suggesting it is a β-sandwich fold similar to that seen in majority of plant viruses.In silicocapsid reconstruction aided understanding of the quaternary organization of subunits in the capsid and molecular interactions present between the subunits. The location of aphid binding EAG motif was identified on the surface loops close to the pentameric axis indicating their role in vector mediated transmission.
A Front-Back Confusion Metric in Horizontal Sound Localization: The FBC Score
Authors: Fischer Tim , Caversaccio Marco , Wimmer Wilhelm 
Published: February 2020

AbstractIn sound localization experiments, currently used metrics for front-back confusion (FBC) analysis weight the occurring FBCs equally, regardless of their deviation from the cone of confusion. To overcome this limitation, we introduce the FBC Score. A sound localization experiment in the horizontal plane with 12 bilaterally implanted cochlear implants (CI) users and 12 normal hearing subjects was performed to validate the method with real clinical data. The overall FBC Rate of the CI users was twice as high as the FBC Score. For the control group, the FBC Rate was 4 times higher than the FBC Score. The results indicate that the FBC Rate is inflated by FBCs that show a considerable deviation from the corresponding value on the cone of confusion.
The major subunit of widespread competence pili exhibits a novel and conserved type IV pilin fold
Authors: Sheppard Devon , Berry Jamie-Lee , Denise Rémi , Rocha Eduardo P. C. , Matthews Steve , Pelicic Vladimir 
Published: February 2020

AbstractType IV filaments (T4F), which are helical assemblies of type IV pilins, constitute a superfamily of filamentous nanomachines virtually ubiquitous in prokaryotes that mediate a wide variety of functions. The competence (Com) pilus is a widespread T4F, mediating DNA uptake (the first step in natural transformation) in bacteria with one membrane (monoderms), an important mechanism of horizontal gene transfer. Here, we report the results of genomic, phylogenetic, and structural analyses of ComGC, the major pilin subunit of Com pili. By performing a global comparative analysis, we show that Com pili genes are virtually ubiquitous in Bacilli, a major monoderm class of Firmicutes. This also revealed that ComGC displays extensive sequence conservation, defining a monophyletic group among type IV pilins. We further report ComGC solution structures from two naturally competent human pathogens,Streptococcus sanguinis(ComGCSS) andStreptococcus pneumoniae(ComGCSP), revealing that this pilin displays extensive structural conservation. Strikingly, ComGCSSand ComGCSPexhibit a novel type IV pilin fold that is purely helical. Results from homology modelling analyses suggest that ComGC unusual structure is compatible with helical filament assembly. Because ComGC displays such a widespread distribution, these results have implications for hundreds of monoderm species.
OTX2 non-cell autonomous activity regulates inner retinal function
Authors: Torero-Ibad Raoul , Mazhar Bilal , Vincent Clémentine , Bernard Clémence , Dégardin Julie , Simonutti Manuel , Lamonerie Thomas , Di Nardo Ariel , Prochiantz Alain , Moya Kenneth L. 
Published: February 2020

AbstractOTX2 is a homeoprotein transcription factor expressed in photoreceptors and bipolar cells in the retina. OTX2, like many other homeoproteins, transfers between cells and exerts non-cell autonomous effects such as promoting survival of retinal ganglion cells that do not express the protein. Here we used a genetic approach to target extracellular OTX2 in the retina by conditional expression of a secreted single chain anti-OTX2 antibody. Compared to control mice, the expression of this antibody by Parvalbumin-expressing neurons in the retina is followed by a reduction in visual acuity in one-month-old mice with no alteration of the retinal structure or cell type number or aspect. A- and b-waves measured by electroretinogram were also indistinguishable from control mice, suggesting no functional deficit of photoreceptors and bipolar cells. Mice expressing the OTX2-neutralizing antibody did show a significant doubling in the flicker amplitude, consistent with a change in inner retinal function. Our results show that interferingin vivowith OTX2 non-cell autonomous activity in the postnatal retina leads to an alteration in inner retinal cell functions and causes a deficit in visual acuity.Significance statementOTX2 is a homeoprotein transcription factor expressed in retinal photoreceptors and bipolar cells. Although theOtx2locus is silent in the inner retina, the protein is detected in cells of the ganglion cell layer consistent with the ability of this class of proteins to transfer between cells. We expressed a secreted single chain antibody (scFv) against OTX2 in the retina to neutralize extracellular OTX2. Antibody expression leads to reduced visual acuity with no change in retinal structure, or photoreceptor or bipolar physiology; however, activity in the inner retina was altered. Thus, interfering with OTX2 non-cell autonomous activity in postnatal retina alters inner retinal function and causes vision loss, highlighting the physiological value of homeoprotein direct non-cell autonomous signaling.
Modulation of spatial cue processing across the lifespan: a geometric polarization of space restores allocentric navigation strategies in children and older adults
Authors: Bécu Marcia , Sheynikhovich Denis , Ramanoël Stephen , Tatur Guillaume , Ozier-Lafontaine Anthony , Sahel José-Alain , Arleo Angelo 
Published: February 2020

AbstractThe impact of development and healthy aging on spatial cognition has been traditionally attributed to a difficulty in using allocentric strategies and a preference for egocentric ones. An alternative possibility, suggested by our previous works, is that this preference is actually conditioned by the spatial cues (e.g. geometric of landmark cues) present in the environment rather than a strategic choice per se. We tested this prediction by having 79 subjects (children, young and older adults) navigating a Y-maze composed either of landmarks or geometric cues, with an immersive head-mounted display that allows us to record both head and eye movements. Our results show that when the performance is based on landmarks solely, children and older adults exhibit a deficit in using allocentric strategies when compared to young adults. Hence, an inverted U-profile of allocentric strategies was observed across the lifespan. This was not due to a default of attention to the landmarks, as evidenced by analysis of gaze dynamics. When geometric were provided, however, older adults and children used allocentric strategies in the same proportion as young adults. They were, in addition, as efficient and quick to implement the strategy. We thus propose a reinterpretation of the previous data in the literature, whereby reference to geometric cues is the default mode for spatial representations, which is immune to age, whereas spatial representations fail to be anchored on landmarks early in development and later in aging. This new interpretation has the potential to reunify several data from the literature, ranging from spatial cues processing to strategy preference, and including other spatial skills like path integration and route learning.
Controlling for the effect of arterial-CO2fluctuations in resting-state fMRI: Comparing end-tidal CO2clamping and retroactive CO2correction
Authors: Golestani Ali M. , Chen J. Jean 
Published: February 2020

AbstractThe BOLD signal, as the basis of functional MRI, arises from both neuronal and vascular factors, with their respective contributions to resting state-fMRI still unknown. Among the factors contributing to “physiological noise”, dynamic arterial CO2fluctuations constitutes the strongest and the most widespread modulator of the grey-matter rs-fMRI signal. Some important questions are: (1) if we were able to clamp arterial CO2such that fluctuations are removed, what would happen to rs-fMRI measures? (2) falling short of that, is it possible to retroactively correct for CO2effects with equivalent outcome? In this study 13 healthy subjects underwent two rs-fMRI acquisition: During the “clamped” run, end-tidal CO2(PETCO2) is clamped to the average PETCO2level of each participant, while during the “free-breathing” run, the PETCO2level is passively monitored but not controlled. PETCO2correction was applied to the free-breathing data by convolving PETCO2with its BOLD response function, and then regressing out the result. We computed the BOLD resting-state fluctuation amplitude (RSFA), as well as seed-independent mean functional connectivity (FC) as the weighted global brain connectivity (wGBC). Furthermore, connectivity between conditions were compared using coupled intrinsic-connectivity distribution (ICD) method. We ensured that PETCO2clamping did not significantly alter heart-beat and respiratory variation. We found that neither PETCO2clamping nor correction produced significant change in RSFA and wGBC. In terms of the ICD, PETCO2clamping and correction both reduced FC strength in the majority of grey matter regions, although the effect of PETCO2correction is considerably smaller than the effect of PETCO2clamping. Furthermore, while PETCO2clamping reduced inter-subject variability in FC, PETCO2correction increased the variability. Overall PETCO2correction is not the equivalent of PETCO2clamping, although it shifts FC values towards the same direction as clamping does.
Traumatic stress history interacts with chronic peripheral inflammation to alter mitochondrial function of synaptosomes in a sex-specific manner
Authors: Shaw Gladys A. , Hyer Molly M. , Targett Imogen , Council Kimaya C. , Dyer Samya K. , Turkson Susie , Burns Chloe M. , Neigh Gretchen N. 
Published: February 2020

AbstractBackgroundRepeated exposures to chronic stress can lead to long lasting negative behavioral and metabolic outcomes. Here, we aim to determine the impact of chronic stress and chronic low-level inflammation on behavior and synaptosomal metabolism.MethodsMale (n = 31) and female (n = 32) C57Bl/6 mice underwent chronic repeated predation stress or daily handling for two rounds of 15 consecutive days of exposure during the adolescent and early adult timeframes. Subsequently, mice were exposed to repeated lipopolysaccharide (LPS; 7.5 x 105EU/kg) or saline injections every third day for eight weeks. Exploratory and social behaviors were assessed in the open field and social interaction tests prior to examination of learning and memory with the Barnes Maze. Mitochondrial function and morphology were assessed in synaptosomes post-mortem. In addition, expression of TNF-α, IL-1ß, and ROMO1 were examined in the hippocampus and prefrontal cortex. Circulating pro- and anti-inflammatory cytokines in the periphery were assessed following the first and last LPS injection as well as at the time of tissue collection. Circulating ROMO1 was assessed in terminal samples.ResultsExposure to repeated predatory stress increased time spent in the corners of the open field, suggestive of anxiety-like behavior, in both males and females. There were no significant group differences in the social interaction test and minimal effects were evident in the Barnes maze. A history of chronic stress interacted with chronic LPS in male mice to lead to a deficit in synaptosomal respiration. Female mice were more sensitive to both chronic stress and chronic LPS such that either a history of chronic stress or a history of chronic LPS was sufficient to disrupt synaptosomal respiration in females. Both stress and chronic LPS were sufficient to increase inflammation and reactive oxygen in males in the periphery and centrally. Females had increased markers of peripheral inflammation following acute LPS but no evidence of peripheral or central increases in inflammatory factors or reactive oxygen following chronic exposures.ConclusionCollectively, these data suggest that while metrics of inflammation and reactive oxygen are disrupted in males following chronic stress and chronic LPS, only the combined condition is sufficient to alter synaptosomal respiration. Conversely, although evidence of chronic inflammation or chronic elevation in reactive oxygen is absent, females demonstrate profound shifts in synaptosomal mitochondrial function with either a history of chronic stress or a history of chronic inflammation. These data highlight that differential mechanisms are likely in play between the sexes and suggest that female sensitivity to neurogenerative conditions may be precipitated by influence of life experiences on mitochondrial function in the synapses.
Hiding in plain sight: structure and sequence analysis reveals the importance of the antibody DE loop for antibody-antigen binding
Authors: Kelow Simon P. , Adolf-Bryfogle Jared , Dunbrack Roland L. 
Published: February 2020

AbstractAntibody variable domains contain “complementarity determining regions” (CDRs), the loops that form the antigen binding site. CDRs1-3 are recognized as the canonical CDRs. However, a fourth loop sits adjacent to CDR1 and CDR2 and joins the D and E strands on the antibody v-type fold. This “DE loop” is usually treated as a framework region, even though mutations in the loop affect the conformation of the CDRs and residues in the DE loop occasionally contact antigen. We analyzed the length, structure, and sequence features of all DE loops in the Protein Data Bank, as well as millions of sequences from HIV-1 infected and naïve patients. We refer to the DE loop as H4 and L4 in the heavy and light chain respectively. Clustering the backbone conformations of the most common length of L4 (6 residues) reveals four conformations: two κ-only clusters, one λ-only cluster, and one mixed κ/λ cluster. The vast majority of H4 loops are length-8 and exist primarily in one conformation; a secondary conformation represents a small fraction of H4-8 structures. H4 sequence variability exceeds that of the antibody framework in naïve human high-throughput sequences, and both L4 and H4 sequence variability from λ and heavy germline sequences exceed that of germline framework regions. Finally, we identified dozens of structures in the PDB with insertions in the DE loop, all related to broadly neutralizing HIV-1 antibodies, as well as antibody sequences from high-throughput sequencing studies of HIV-infected individuals, illuminating a possible role in humoral immunity to HIV-1.
Wireless Programmable Recording and Stimulation of Deep Brain Activity in Freely Moving Humans
Authors: Topalovic Uros , Aghajan Zahra M. , Villaroman Diane , Hiller Sonja , Christov-Moore Leonardo , Wishard Tyler J. , Stangl Matthias , Hasulak Nicholas R. , Inman Cory , Fields Tony A. , Eliashiv Dawn , Fried Itzhak , Suthana Nanthia 
Published: February 2020

AbstractCurrent implantable devices that allow for recording and stimulation of brain activity in humans are not inherently designed for research and thus lack programmable control and integration with wearable sensors. We developed a platform that enables wireless and programmable intracranial electroencephalographic recording and deep brain stimulation integrated with wearable technologies. This methodology, when used in freely moving humans with implanted neural devices, can provide an ecologically valid environment conducive to elucidating the neural mechanisms underlying naturalistic behaviors and developing viable therapies for neurologic and psychiatric disorders.