bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal Odor Reduces the Neural Response to Fearful Faces in Human Infants
Authors: Jessen Sarah 
Published: November 2019

AbstractMaternal odor is known to play an important role in mother-infant-interaction in many altricial species such as rodents. However, we only know very little about its role in early human development. The present study therefore investigated the impact of maternal odor on infant brain responses to emotional expression. We recorded the electroencephalographic (EEG) signal of seven-month-old infants watching happy and fearful faces. Infants in two control groups exposed to no specific odor (control 1) or the odor of a different infant’s mother (control 2) showed the expected EEG fear response. Crucially, this response was markedly absent in the experimental group exposed to their mother’s odor. Thus, infants respond differently to fear signals in the presence of maternal odor. Our data therefore suggest that maternal odor can be a strong modulator of social perception in human infants.
Nutrient sensing; transcriptomic response and regulation of gut motility in an agastric vertebrate
Authors: Le Hoang T. M. D. , Lie Kai K. , Etayo Angela , Rønnestad Ivar , Sæle Øystein 
Published: November 2019

AbstractThe transcriptome of nutrient sensing and the regulation of gut motility by nutrients in a stomachless fish with a short digestive tract; the ballan wrasse (Labrus berggylta) were investigated. Using an in vitro model, we differentiate how signals initiated by physical stretch and nutrients modulate the gut evacuation rate and motility patterns, and transcriptomic changes. Stretch on the intestine by inert cellulose initiated fast evacuation out of the anterior intestine compared to the digestible protein and lipid. Stretch on the intestine upregulated genes associated with increased muscle activity, whereas nutrients stimulated pathways related to ribosomal activity and the increase in the expression of several neuropeptides which are directly involved in gut motility regulation. Our findings show that physical pressure in the intestine initiate contractions propelling the matter towards the exit, whereas the sensing of nutrients modulates the motility to prolong the residence of digesta in the digestive tract for optimal digestion.Summary statementPressure by food speed up peristalsis in the intestine, but the intestines ability to sense nutrients slow down peristalsis for better digestion. This is partly controlled by genetic regulation.
A model to study orienting responses in zebrafish, and applications towards the emotion-cognition interaction
Authors: do Nascimento Bianca Gomes , Oliveira e Oliveira Hingrid Suzzan Tarso , Lima Silva Hadda Tercya , de Siqueira-Silva Diógenes Henrique , Lima-Maximino Monica , Maximino Caio 
Published: November 2019

AbstractOrienting responses (ORs) are whole-organism reflexes that are elicited by innocuous stimuli, and which decrease in magnitude after stimulus repetition. ORs represent relatively simple responses that can be used to study attentional processes, and are modulated by the organism’s state, including arousal and activation levels, as well as by emotional processes. Here we describe a simple method to study ORs in zebrafish, a model organism increasingly being used in behavioural neuroscience. After presentation of a static visual stimulus, an OR is elicited, characterized by approaching the stimulus and orienting towards it. After repeated stimulation, OR decreases, suggesting habituation. These responses are qualitatively altered by exposure to a fear-eliciting alarm substance (i.e., derived from the skin of a conspecific), since exposed animals avoid the visual stimulus and orient either away from the stimulus or towards it, but at a distance. The protocol can be used to study orienting responses, as well as the impact of fear and arousal on these reflexes.
Kinetic Analysis of Lipid Metabolism in Live Breast Cancer Cells via Nonlinear Optical Microscopy
Authors: Hou J. , Reid N. E. , Tromberg B. J. , Potma E. O. 
Published: November 2019

AbstractInvestigating the behavior of breast cancer cells via reaction kinetics may help unravel the mechanisms that underlie metabolic changes in tumors. However, obtaining human in vivo kinetic data is challenging due to difficulties associated with measuring these parameters. Non-destructive methods of measuring lipid content in live cells, provide a novel approach to quantitatively model lipid synthesis and consumption. In this study, two-photon excited fluorescence (TPEF) was used to determine metabolic rates via the cell’s optical redox ratio (ORR) as reported by fluorescence intensity ratios of metabolic coenzymes, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD+). Concurrently, coherent Raman scattering (CRS) microscopy was used to probe de novo intracellular lipid content. Combining non-linear optical microscopy and Michaelis-Menten-kinetics based simulations, we isolated fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells. When treated with 17β-Estradiol (E2), cancer cells showed a 3-fold increase in beta-oxidation rate as well as a 50% increase in cell proliferation rate. Similarly, the rate of de novo lipid synthesis in cancer cells treated with E2 was increased by 60%. Furthermore, we treated T47D cells with etomoxir (ETO) and observed that cancer cells treated with ETO exhibited a ∼70% reduction in β-oxidation. These results show the ability to probe lipid alterations in live cells with minimum interruption, to characterize both glucose and lipid metabolism in breast cancer cells via quantitative kinetic models and parameters.Statement of SignificanceCombining non-linear optical microscopy (NLOM) and deuterium labeling provides insight into lipid metabolism in live cancer cells during cancer development and progression. The dynamic metabolic data is modelled with Michaelis-Menten-kinetics to independently quantify the lipid synthesis and utilization in cancer cells. Changes in lipid levels are found to originate from de novo lipid synthesis using glucose as a source, lipid consumption from β-oxidation and lipid consumption from cell proliferation, processes that can separately analyzed with the Michaelis-Menten model. In this work, we isolate fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells in response to estradiol stimulation and etomoxir treatment, dynamic processes that cannot be easily observed without the application of appropriate models.
Assessment of anesthesia on physiological stability and bold signal reliability during visual or acoustic stimulation in the cat
Authors: Levine Alexandra , Li Benson , Barnes Paisley , Lomber Stephen G. , Butler Blake E. 
Published: November 2019

AbstractBackgroundNeuroimaging methods including fMRI provide powerful tools to observe whole-brain functional networks. This is particularly powerful in animal models, allowing these networks to be probed using complementary methods. However, most animals must be anesthetized for neuroimaging, giving rise to complications resulting from anesthetic effects on the animal’s physiological and neurological functions. For example, an established protocol for feline neuroimaging involves co-administration of ketamine and isoflurane – the latter of which is known to suppress cortical function.New MethodHere, we compare this established protocol to alfaxalone, a single-agent anesthetic for functional neuroimaging. We first compare the two in a controlled environment to assess relative safety and to measure physiological stability over an extended time window. We then compare patterns of auditory and visually-evoked activity measured at 7T to assess mean signal strength and between-subjects signal variability.Results in Comparison with Existing MethodsWe show that alfaxalone results in more stable respiratory rates over the 120 minutes testing period, with evidence of smaller between measurements variability within this time window, when compared to ketamine plus isoflurane. Moreover, we demonstrate that both agents evoke similar mean BOLD signals across animals, but that alfaxalone elicits more consistent BOLD activity in response to sound stimuli across all ROIs observed.ConclusionsAlfaxalone is observed to be more physiologically stable, evoking a more consistent BOLD signal across animals than the co-administration of ketamine and isoflurane. Thus, an alfaxalone-based protocol may represent a better approach for neuroimaging in animal models requiring anesthesia.
The thrombopoietin receptor agonist eltrombopag inhibits human cytomegalovirus replication via iron chelation
Authors: Vogel Jens-Uwe , Schmidt Sophie , Schmidt Daniel , Rothweiler Florian , Koch Benjamin , Baer Patrick C. , Rabenau Holger F. , Michel Detlef , Stamminger Thomas , Michaelis Martin , Cinatl Jindrich 
Published: November 2019

AbstractThe thrombopoietin receptor agonist eltrombopag was successfully used against human cytomegalovirus (HCMV)-associated thrombocytopenia refractory to immunomodulatory and antiviral drugs. These effects were ascribed to effects of eltrombopag on megakaryocytes. Here, we tested whether eltrombopag may also exert direct antiviral effects. Therapeutic eltrombopag concentrations inhibited HCMV replication in human fibroblasts and adult mesenchymal stem cells infected with six different virus strains and drug-resistant clinical isolates. Eltrombopag also synergistically increased the anti-HCMV activity of the mainstay drug ganciclovir. Time-of-addition experiments suggested that eltrombopag interferes with HCMV replication after virus entry. Eltrombopag was effective in thrombopoietin receptor-negative cells, and addition of Fe3+prevented the anti-HCMV effects, indicating that it inhibits HCMV replication via iron chelation. This may be of particular interest for the treatment of cytopenias after haematopoietic stem cell transplantation, as HCMV reactivation is a major reason for transplantation failure. Since therapeutic eltrombopag concentrations are effective against drug-resistant viruses and synergistically increase the effects of ganciclovir, eltrombopag is also a drug repurposing candidate for the treatment of therapy-refractory HCMV disease.
Spermiogenesis in the acoelSymsagittifera roscoffensis: nucleus-plasma membrane contact sites and microtubules
Authors: Hayes Matthew J. , Zakrzewski Anne-C. , Levine Tim P. , Telford Maximilian J. 
Published: November 2019

AbstractSymsagittifera roscoffensisis a small marine worm found in the intertidal zone of sandy beaches around the European shores of the Atlantic.S. roscoffensisis a member of the Acoelomorpha, a group of flatworms formerly classified with the Platyhelminthes, but now recognised as Xenacoelomorpha, a separate phylum of disputed affinity. We have used electron microscopy to examine the process of spermiogenesis (the final stage of spermatogenesis) inS. roscoffensis, by which spermatids form highly elongated spermatozoa. Their nuclei are long and thread-like, running most of the cell’s length and during the process a pair of flagella are fully incorporated into the cell body. Two previously undescribed inter-organelle contact sites form at different stages of spermiogenesis. Strikingly, there is an extensive nucleus-plasma membrane contact site. Golgi-derived granules containing electron-dense filaments line up along the spermatid plasma membrane, undergo a conformational change, and donate material that forms a peri-nuclear layer that cements this contact site. We also show in earlier stage spermatids that the same granules are associated with microtubules, presumably for traffic along the elongating cell. We identify a second spermiogenesis-specific contact site where sheaths engulfing each internalising flagellum contact the nuclear envelope. Finally, detailed studies of the spermatozoon axonemes show that the central keel has varying numbers of microtubules along the length of the cell, and is likely to be a centriole derivative.Summary sentenceDuring spermiogenesis in the acoel flatwormSymsagittifera roscoffensis,two previously unidentified contact sites contribute to the structure of the mature spermatozoon and the axonemal structures show direct continuity between doublet and dense core microtubules.
Impaired Hippocampal-cortical interactions during sleep and memory reactivation without consolidation in a mouse model of Alzheimer’s disease
Authors: Benthem S. D. , Skelin I. , Moseley S. C. , Dixon J. R. , Melilli A. S. , Molina L. , McNaughton B. L. , Wilber A. A. 
Published: November 2019

AbstractSpatial learning is impaired in preclinical Alzheimer’s disease (AD). We reported similar impairments in 3xTg-AD mice learning aspatial reorientation task. Memory reactivation during sleep is critical for learning related plasticity, and memory consolidation is correlated with hippocampal sharp wave ripple (SWR) density, cortical delta waves (DWs), and their temporal coupling - postulated as a physiological substrate of memory consolidation. Finally, hippocampal-cortical dyscoordination is prevalent in individuals with AD. Thus, we hypothesized impaired memory consolidation mechanisms in hippocampal-cortical networks could account for spatial memory deficits. We assessed sleep architecture, SWR/DW dynamics and memory reactivation in a mouse model of tauopathy and amyloidosis implanted with a recording array targeting isocortex and hippocampus. Mice underwent daily recording sessions of rest-task-rest while learning thespatial reorientation task. We assessed memory reactivation by matching activity patterns from the approach to the unmarked reward zone to patterns during slow wave sleep (SWS). AD mice had more SWS, but reduced SWR density. The increased SWS compensated for reduced SWR density so there was no reduction in SWR number. Conversely, DW density was not reduced so the number of DWs was increased. In control mice hippocampal SWR-cortical DW coupling was strengthened in post-task-sleep and was correlated with performance on thespatial reorientation taskthe following day. However, in AD mice SWR-DW coupling was reduced and not correlated with behavior, suggesting behavioral decoupling. Thus, reduced SWR-DW coupling may cause impaired learning in AD and may serve as a biomarker for early AD related changes.Significance StatementUnderstanding the relationship between network dynamics and cognition early in Alzheimer’s disease progression is critical for identifying therapeutic targets for earlier treatment. We assessed hippocampal-cortical interactions during sleep in AD mice as a potential cause of early spatial learning and memory deficits. We identified compensatory sleep changes in AD mice, that ameliorated some brain dysfunction. Despite the compensatory changes, impaired spatial navigation and impaired hippocampal–cortical (sharp wave ripple-delta wave) interactions were apparent in AD mice. In control but not AD mice hippocampal-cortical interactions were correlated with performance on the spatial task, the following day, suggesting a potential mechanism of impaired consolidation in AD mice. Thus, changes in hippocampal-cortical brain dynamics during sleep may underlie early memory deficits in AD.
Protein function achieved through multiple covalent states
Authors: Butera Diego , Hogg Philip J. 
Published: November 2019

AbstractThe structure of proteins is defined by two main types of covalent bonds; the peptide bonds that link the amino acid residues and disulfide bonds that link pairs of cysteine amino acids. Disulfide bonds are introduced during protein folding and their formation is assumed to be complete in the mature, functional protein. We tested this assumption by quantifying the redox state of disulfide bonds in human blood proteins in their native environment. Using a differential cysteine alkylation and mass spectrometry method, we measured the redox state of disulfide bonds in circulating fibrinogen and von Willebrand factor. There is an extraordinary disulfide lability in the proteins, with 27 bonds in the two proteins ranging from 3 to 50% reduced in healthy human donors. Modelling of the data indicates that the proteins exist in hundreds of different disulfide-bonded states in the circulation. Different covalent states of fibrinogen are associated with different binding activities and their distribution is changed by fluid shear forces and altered in patients with cardiovascular disease, indicating that the different states have different functions and are dynamic. These findings have implications for protein function generally and how proteins are targeted in experimental settings and for therapeutic purposes.
Spatiotemporal patterns of rodent hippocampal field potentials uncover spatial representations
Authors: Cao Liang , Varga Viktor , Chen Zhe S. 
Published: November 2019

AbstractSpatiotemporal patterns of large-scale spiking and field potentials of the rodent hippocampus encode spatial representations during maze run, immobility and sleep. Here, we showed that multi-site hippocampal field potential amplitude at ultra-high frequency band (FPAuhf) provides not only a fast and reliable reconstruction of the rodent’s position in wake, but also a readout of replay content during sharp wave ripples. This FPAuhf feature may serve as robust real-time decoding strategy from large-scale (up to 100,000 electrodes) recordings in closed-loop experiments. Furthermore, we developed unsupervised learning approaches to extract low-dimensional spatiotemporal FPAuhf features during run and ripple periods, and to infer latent dynamical structures from lower-rank FPAuhf features. We also developed a novel optical flow-based method to identify propagating spatiotemporal LFP patterns from multi-site array recordings, which can be used for decoding application. Finally, we developed a prospective decoding strategy to predict animal’s future decision in goal-directed navigation.
Pregnancy alters innate immune responses to Zika virus infection in the genital tract
Authors: Lesteberg Kelsey E. , Fader Dana S. , Beckham J. David 
Published: November 2019

AbstractRecent outbreaks of Zika virus (ZIKV) have been associated with birth defects, including microcephaly and neurological impairment. However, the mechanisms which confer increased susceptibility to ZIKV during pregnancy remain unclear. We hypothesized that poor outcomes from ZIKV infection during pregnancy are due in part to pregnancy-induced alteration of innate immune cell frequencies and cytokine expression. To examine the impact of pregnancy on innate immune responses, we inoculated pregnant and non-pregnant female C57BL/6 mice with 5×105FFU of ZIKV intravaginally. Innate immune cell frequencies and cytokine expression were measured by flow cytometry at day 3 post infection. Compared to non-pregnant mice, pregnant mice exhibited higher frequencies of uterine macrophages (CD68+) and tolerogenic dendritic cells (CD11c+ CD103+ and CD11c+ CD11b+). Additionally, ZIKV-infected pregnant mice had lower frequencies of CD45+ IL-12+ and CD11b+ IL-12+ cells in the uterus and spleen. These data show that pregnancy results in an altered innate immune response to ZIKV infection in the genital tract of mice and that pregnancy-associated immune modulation may play an important role in the severity of acute ZIKV infection.ImportancePregnant females longer duration that viremia following infection with Zika virus but the mechanism of this is not established. Innate immune cellular responses are important for controlling virus infection and are important for development and maintenance of pregnancy. Thus, the acute immune response to Zika virus during pregnancy may be altered so that the pregnancy can be maintained. To examine this interaction, we utilized a mouse model of Zika virus infection during pregnancy using intravaginal inoculation. We found that following Zika virus infection, pregnant mice exhibited increased expression of tolerant or non-inflammatory dendritic cells. Additionally, we found that pregnant mice have significantly depressed ability to secrete the cytokine IL-12 from innate immune cells in the uterus and the spleen while maintaining MHCII expression. These findings show that pregnancy-induced changes in the innate immune cells are biased towards tolerance and can result in decreased antigen-dependent stimulation of immune responses.
Six cases of perforating pilomatricoma: Anetodermic changes with expression of matrix metalloproteinases
Authors: Watabe Daisuke , Mori Shiho , Akasaka Toshihide , Motegi Sei‐ichiro , Ishikawa Osamu , Amano Hiroo 
Published: November 2019

AbstractPerforating pilomatricoma (PP) is a rare clinical variant of pilomatricoma presenting as a crusted or ulcerated nodule. Previous reports have suggested that the tumor cells perforate the epidermis through a process of transepithelial elimination. Here, we report six cases of PP and examine the mechanism of transepithelial elimination in PP. Histologically, the dermis above or around the tumor nest exhibited edema, dilated vascular spaces, sparse collagen bundles and absence of elastic fibers, suggesting anetodermic changes in all cases. Immunohistochemistry demonstrated many CD68‐positive macrophages around the tumor nests. Matrix metallopeptidase (MMP)‐9 and MMP‐12 were expressed in the inflammatory cells and tumor cells, and were also present in the epidermis and fibroblasts in all cases. We speculate that in PP anetodermic change caused by MMP and elastases including MMP‐9 and MMP‐12 may precede elimination of the tumor.
Behavioural complementarity among frugivorous birds and lizards can promote plant diversity in island ecosystems
Authors: Morán‐López Teresa , González‐Castro Aarón , Morales Juan Manuel , Nogales Manuel 
Published: November 2019

Abstract

The behavioural complementarity of fruit‐eating animals is thought to exert a key role in plant community assembly. However, a mechanistic understanding of the causal links between the two processes is still lacking.

This study assesses whether complementarity between dispersers in feeding and microhabitat‐use behaviour enhances community‐scale dispersal services, resulting in a more diverse community of seedlings.

We used a Bayesian approach to connect a comprehensive database of seed dispersal effectiveness at a community scale with a transition probability model that accounts for behavioural complementarity. Our model system was the thermosclerophyllous shrubland of the Canary Islands. There, fleshy‐fruited plants rely on two types of frugivores: lizards and birds.

Lizards consumed all plant species and preferentially used open areas, whereas birds foraged for small single‐seeded fruits and dispersed their seeds beneath plants. Through feeding on different sets of plants, they generated a rich seed‐rain community. By diversifying the microhabitat of deposition, more species could find suitable recruitment sites.

Distinct foraging and microhabitat‐use choices led to complementary dispersal services. Lizards ensured that all plant species were present in the seedling community, while birds promoted a more even distribution of them. As a result, diversity in the community of seedlings was enhanced.

Overall, our work underscores that behavioural complementarity promotes diversity in the early‐regenerating plant communities. These enhanced dispersal services rely on the presence of all functional groups. Thus, in communities where frugivores display unique behaviours, preserving a diverse community of dispersers should be a conservation target.

A free Plain Language Summary can be found within the Supporting Information of this article.