bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotional valence modulates the topology of the parent-infant inter-brain network
Authors: Santamaria Lorena , Noreika Valdas , Georgieva Stanimira , Clackson Kaili , Wass Sam , Leong Victoria 
Published: May 2019

ABSTRACTEmotional communication between parents and children is crucial during early life, yet little is known about its neural underpinnings. Here, we adopt a dual-brain connectivity approach to assess how emotional valence modulates the parent-infant neural network. Fifteen mothers modelled positive and negative emotions toward pairs of objects during social interaction with their infants (aged 10.3 months) whilst their neural activity was concurrently measured using dual-EEG. Intra-brain and inter-brain network connectivity in the 6-9 Hz (infant Alpha) range was computed during maternal expression of positive and negative emotions using directed (partial directed coherence) and non-directed (phase-locking value) connectivity metrics. Graph theoretical metrics were used to quantify differences in network topology as a function of emotional valence. Inter-brain network indices (Density, Strength and Divisibility) consistently revealed that the integration of parents’ and childrens’ neural processes was significantly stronger during maternal demonstrations of positive than negative emotions. Further, directed inter-brain metrics indicated that mother-to-infant directional influences were stronger during the expression of positive than negative emotions. These results suggest that the parent-infant inter-brain network is modulated by the emotional quality and tone of dyadic social interactions, and that inter-brain graph metrics may be successfully applied to examine these changes in interpersonal network topology.
Growth defects and loss-of-function in synthetic gene circuits
Authors: Nikolados Evangelos-Marios , Weiße Andrea Y. , Ceroni Francesca , Oyarzún Diego A. 
Published: May 2019

AbstractSynthetic gene circuits perturb the physiology of their cellular host. The extra load on endogenous processes shifts the equilibrium of resource allocation in the host, leading to slow growth and reduced biosynthesis. Here we built integrated host-circuit models to quantify growth defects caused by synthetic gene circuits. Simulations reveal a complex relation between circuit output and cellular capacity for gene expression. For weak induction of heterologous genes, protein output can be increased at the expense of growth defects. Yet for stronger induction, cellular capacity reaches a tipping point, beyond which both gene expression and growth rate drop sharply. Extensive simulations across various growth conditions and large regions of the design space suggest that the critical capacity is a result of ribosomal scarcity. We studied the impact of growth defects on various gene circuits and transcriptional logic gates, which highlights the extent to which cellular burden can limit, shape and even break down circuit function. Our approach offers a comprehensive framework to assess the impact of host-circuit interactions in silico, with wide-ranging implications for the design and optimization of bacterial gene circuits.
A transient time window for early predispositions in newborn chicks
Authors: Versace Elisabetta , Ragusa Morgana , Vallortigara Giorgio 
Published: May 2019

AbstractNeonates of different species are born with a set of predispositions that influence their early orienting responses toward the first stimuli encountered in their life. Human neonates and domestic chicks exhibit several similarities in the predisposition for attending to objects that move with speed changes, face-like stimuli and biological motion. Although early predispositions are connected to physiological development, little is known on the temporal course of early predispositions (whether they are stable or change in time) and on their genetic basis. To address these issues, we tested the preference for objects that change in speed vs. linear motion in three chicken breeds (Padovana, Polverara and Robusta maculata) within one day after hatching and three days after hatching. We found that the predisposition to preferentially attend to changes in speed is fixed at the species level on the first day of life and that it disappears by day three. These results indicate the existence of a short and transient time window of early predispositions that does not depend on visual experience.
Treatment-seeking for vaginal fistula in sub-Saharan Africa
Authors: Gebremedhin Samson , Asefa Anteneh 
Published: May 2019

AbstractBackgroundThere is dearth of data regarding the treatment-seeking practice of women living with vaginal fistula. The paper describes the health-seeking behaviour of fistula cases in the sub-Saharan Africa (SSA) where the burden of the problem is high.MethodsWe analysed the data of 1,317 women who ever experienced vaginal fistula, extracted from 16 national Demographic and Health Surveys carried out in SSA between 2010 and 2017. The association between treatment-seeking and basic socio-demographic characteristics assessed via mixed-effects logistic regression and the outputs are provided using adjusted odds ratio (AOR) with 95% confidence intervals (CI).ResultsTwo-thirds (67.6%) of the women encountered the fistula soon after delivery implying obstetric fistula. Fewer identified sexual assault (3.8%) and pelvic surgery (2.7%) as the cause. In 25.8% of the cases clear-cut causes couldn’t be ascertained and excluding these ambiguous causes, 91.2% of the women had obstetric fistula. Among those who ever had fistula, 60.3% (95% CI: 56.9-63.6%) sought treatment and 28.5% (95% CI: 25.3-31.6%) underwent fistula-repair surgery. The leading reasons for not seeking treatment were: unaware that it can be repaired (21.4%), don’t know where to get the treatment (17.4%), economic constraints (11.9%), healed by itself (11.9%) and embarrassment (7.9%). The regression analysis indicated, teenagers as compared to adults 35 years or older [AOR=0.31 (95 % CI: 0.20-47)]; and women devoid of formal education when compared to women with any formal education [AOR=0.69 (95% CI: 0.51-0.93)], had reduced odds of treatment-seeking. In 25.9% of the women who underweight fistula-repair surgery, complete continence after surgery was not achieved.ConclusionTreatment-seeking for fistula remains low and it should be augmented via mix of strategies for abridging health-system, psycho-social, economic and awareness barriers.
Parasite-induced shifts in host movement may explain the transient coexistence of high- and low-pathogenic disease strains
Authors: Fofana Abdou Moutalab , Hurford Amy 
Published: May 2019

AbstractMany parasites induce decreased host movement, known as lethargy, which can impact disease spread and the evolution of virulence. Mathematical models have investigated virulence evolution when parasites cause host death, but disease-induced decreased host movement has received relatively less attention. Here, we consider a model where, due to the within-host parasite replication rate, an infected host can become lethargic and shift from a moving to a resting state, where it can die. We find that when the lethargy and disease-induced mortality costs to the parasites are not high, then evolutionary bistability can arise, and either moderate or high virulence can evolve depending on the initial virulence and the magnitude of mutation. These results suggest, firstly, the transient coexistence of strains with different virulence, which may explain the coexistence of low- and high-pathogenic strains of avian influenza and human immunodeficiency viruses, and secondly, that medical interventions to treat the symptoms of lethargy or prevent disease-induced host deaths can result in a large jump in virulence and the rapid evolution of high virulence. In complement to existing results that show bistability when hosts are heterogeneous at the population-level, we show that evolutionary bistability may arise due to transmission heterogeneity at the individual host-level.
Multi-trait genome-wide association meta-analysis of dietary intake identifies new loci and genetic and functional links with metabolic traits
Authors: Merino Jordi , Dashti Hassan S. , Sarnowski Chloé , Lane Jacqueline M. , Udler Miriam S. , Todorov Petar V. , Song Yanwei , Wang Heming , Kim Jaegil , Tucker Chandler , Campbell John , Tanaka Toshiko , Chu Audrey Y. , Tsai Linus , Pers Tune H. , Chasman Daniel I. , Dupuis Josée , Rutter Martin K. , Florez Jose C. , Saxena Richa 
Published: May 2019

ABSTRACTDietary intake, a major contributor to the global obesity epidemic1–5, is a complex phenotype partially affected by innate physiological processes.6–11 However, previous genome-wide association studies (GWAS) have only implicated a few loci in variability of dietary composition.12–14 Here, we present a multi-trait genome-wide association meta-analysis of inter-individual variation in dietary intake in 283,119 European-ancestry participants from UK Biobank and CHARGE consortium, and identify 96 genome-wide significant loci. Dietary intake signals map to different brain tissues and are enriched for genes expressed in β1-tanycytes and serotonergic and GABAergic neurons. We also find enrichment of biological pathways related to neurogenesis. Integration of cell-line and brain-specific epigenomic annotations identify 15 additional loci. Clustering of genome-wide significant variants yields three main genetic clusters with distinct associations with obesity and type 2 diabetes (T2D). Overall, these results enhance biological understanding of dietary composition, highlight neural mechanisms, and support functional follow-up experiments.
Water for sterol: an unusual mechanism of sterol egress from a StARkin domain
Authors: Khelashvili George , Pandey Kalpana , Chauhan Neha , Eliezer David , Menon Anant K. 
Published: May 2019

AbstractPreviously we identified a new family of endoplasmic reticulum membrane proteins that possess sterol-binding StARkin domains (Gatta et al. eLife 2015). These Lam/GramD1 proteins are implicated in intracellular sterol homeostasis, a function that requires them to be able to bind sterols. Here we show how these proteins exchange sterol molecules with membranes. An aperture at one end of the StARkin domain enables sterol to enter/exit the binding pocket. Strikingly, the wall of the pocket is fractured along its length, exposing bound sterol to solvent. We considered whether hydration of the pocket could mediate sterol entry/exit. Large-scale atomistic molecular dynamics simulations reveal that sterol egress involves widening of the fracture, penetration of water into the cavity and consequent destabilization of the bound sterol. The simulations also identify polar residues along the fracture that are important for sterol release. Their replacement with alanine affects the ability of the StARkin domain to bind sterol, catalyze inter-vesicular sterol exchange and alleviate the nystatin-sensitivity of lam2Δ yeast cells. These data suggest an unprecedented, water-controlled mechanism of sterol acquisition and discharge from a StARkin domain.
Targeted photostimulation uncovers circuit motifs supporting short-term memory
Authors: Daie Kayvon , Svoboda Karel , Druckmann Shaul 
Published: May 2019

AbstractShort-term memory is associated with persistent neural activity without sustained input, arising from the interactions between neurons with short time constants1,2. A variety of neural circuit motifs could account for measured neural activity3–7. A mechanistic understanding of the neural circuits supporting short-term memory requires probing network connectivity between functionally characterized neurons8. We performed targeted photostimulation of small (< 10) groups of neurons, while imaging the response of hundreds of other neurons9,10, in anterior-lateral motor cortex (ALM) of mice performing a delayed response task11. Mice were instructed with brief auditory stimuli to make directional movements (lick left or lick right), but only after a three second delay epoch. ALM contains neurons with delay epoch activity that is selective for left or right choices. Targeted photostimulation of groups of neurons during the delay epoch allowed us to observe the functional organization of population activity and recurrent interactions underlying short-term memory. These experiments revealed strong coupling between neurons sharing similar selectivity. Brief photostimulation of functionally related neurons produced changes in activity in sparse subpopulations of nearby neurons that persisted for several seconds following stimulus offset, far outlasting the duration of the perturbation. Photostimulation produced behavioral biases that were predictable based on the selectivity of the perturbed neuronal population. These results suggest that ALM contains multiple intercalated modules, consisting of recurrently coupled neurons, that can independently maintain persistent activity.
Lipocalin-2 is a Sensitive and Specific Marker of Bacterial Infection in Children
Authors: Herberg Jethro , Huang Honglei , Thezenas Marie L. , Janes Victoria , Carter Michael , Gormley Stuart , Hamilton Melisa S. , Kessler Benedikt , Levin Michael , Casals-Pascual Climent 
Published: May 2019

AbstractIntroductionBacterial infection is the leading cause of death in children globally. Clinical algorithms to identify children who are likely to benefit from antimicrobial treatment remain suboptimal. Biomarkers that accurately identify serious bacterial infection (SBI) could improve diagnosis and clinical management. Lipocalin 2 (LCN2) and neutrophil collagenase (MMP-8) are neutrophil-derived biomarkers associated with bacterial infection.MethodsWe evaluated LCN2 and MMP-8 as candidate biomarkers in 40 healthy controls and 151 febrile children categorised confirmed SBI, probable SBI, or viral infection. The diagnostic performance of LCN2 and MMP-8 to predict SBI was estimated by the area under the receiver operating characteristic curve (AUROC) and compared to the performance of C-reactive protein (CRP).ResultsPlasma LCN2 and MMP-8 concentration were predictive of SBI. The AUROC (95% CI) for LCN2, MMP8 and CRP to predict SBI was 0.88 (0.82-0.94); 0.80 (0.72-0.87) and 0.89 (0.84-0.94), respectively. The diagnostic performance of LCN2 in combination with CRP was significantly superior to either marker alone: AUROC 0.92 (95% CI: 0.88-0.96).ConclusionLCN2 is a sensitive and specific predictor of SBI in children which could be used to improve clinical management and antimicrobial stewardship. LCN2 should be further evaluated in prospective clinical studies.
Impulse responses reveal unimodal and bimodal access to visual and auditory working memory
Authors: Wolff M. J. , Kandemir G. , Stokes M. G. , Akyürek E. G. 
Published: May 2019

AbstractIt is unclear to what extent sensory processing areas are involved in the maintenance of sensory information in working memory (WM). Previous studies have thus far relied on finding neural activity in the corresponding sensory cortices, neglecting potential activity-silent mechanisms such as connectivity-dependent encoding. It has recently been found that visual stimulation during visual WM maintenance reveals WM-dependent changes through a bottom-up neural response. Here, we test whether this impulse response is uniquely visual and sensory-specific. Human participants (both sexes) completed visual and auditory WM tasks while electroencephalography was recorded. During the maintenance period, the WM network was perturbed serially with fixed and task-neutral auditory and visual stimuli. We show that a neutral auditory impulse-stimulus presented during the maintenance of a pure tone resulted in a WM-dependent neural response, providing evidence for the auditory counterpart to the visual WM findings reported previously. Interestingly, visual stimulation also resulted in an auditory WM-dependent impulse response, implicating the visual cortex in the maintenance of auditory information, either directly, or indirectly as a pathway to the neural auditory WM representations elsewhere. In contrast, during visual WM maintenance only the impulse response to visual stimulation was content-specific, suggesting that visual information is maintained in a sensory-specific neural network, separated from auditory processing areas.Significance StatementWorking memory is a crucial component of intelligent, adaptive behaviour. Our understanding of the neural mechanisms that support it has recently shifted: rather than being dependent on an unbroken chain of neural activity, working memory may rely on transient changes in neuronal connectivity, which can be maintained efficiently in activity-silent brain states. Previous work using a visual impulse stimulus to perturb the memory network has implicated such silent states in the retention of line orientations in visual working memory. Here, we show that auditory working memory similarly retains auditory information. We also observed a sensory-specific impulse response in visual working memory, while auditory memory responded bi-modally to both visual and auditory impulses, possibly reflecting visual dominance of working memory.
A novel mechanism for amplification of sensory responses by the amygdala-TRN projections
Authors: Aizenberg Mark , Martinez Solymar Rolon , Pham Tuan , Rao Winnie , Haas Julie , Geffen Maria N. 
Published: May 2019

AbstractMany forms of behavior require selective amplification of neuronal representations of relevant environmental signals. Following emotional learning, sensory stimuli drive enhanced responses in the sensory cortex. However, the brain circuits that underlie emotionally driven control of the sensory representations remain poorly understood. Here we identify a novel pathway between the basolateral amygdala (BLA), an emotional learning center in the mouse brain, and the inhibitory nucleus of the thalamus (TRN). We demonstrate that activation of this pathway amplifies sound-evoked activity in the central auditory pathway. Optogenetic activation of BLA suppressed spontaneous, but not tone-evoked activity in the auditory cortex (AC), effectively amplifying tone-evoked responses in AC. Anterograde and retrograde viral tracing identified robust BLA projections terminating at TRN. Optogenetic activation of amygdala-TRN pathway mimicked the effect of direct BLA activation, amplifying tone-evoked responses in the auditory thalamus and cortex. The results are explained by a computational model of the thalamocortical circuitry. In our model, activation of TRN by BLA suppresses spontaneous activity in thalamocortical cells, and as a result, thalamocortical neurons are primed to relay relevant sensory input. These results demonstrate a novel circuit mechanism for shining a neural spotlight on behaviorally relevant signals and provide a potential target for treatment of neuropsychological disorders, in which emotional control of sensory processing is disrupted.
Significant enrichment of Herpesvirus interactors in GWAS data suggests causal inferences for the association between Epstein Barr virus and multiple sclerosis
Authors: Mechelli Rosella , Umeton Renato , Srinivasan Sundararajan , Fornasiero Arianna , Ferraldeschi Michela ,   IMSGC and WTCCC2, Centonze Diego , Farina Cinthia , Salvetti Marco , Ristori Giovanni 
Published: May 2019

SUMMARYWe exploited genetic information to assess the role of non-genetic factors in multifactorial diseases. To this aim we isolated candidate “interactomes” (i.e. groups of genes whose products are known to physically interact with environmental exposures and biological processes, plausibly relevant for disease pathogenesis) and analyzed nominal statistical evidence of association with genetic predisposition to multiple sclerosis (MS) and other inflammatory and non-inflammatory complex disorders. The interaction between genotype and Herpesviruses emerged as specific for MS, with Epstein Barr virus (EBV) showing higher levels of significance compared to Human Herpesvirus 8 (HHV8) and, more evidently, to cytomegalovirus (CMV). In accord with this result, when we classified the MS-associated genes contained in the interactomes into canonical pathways, the analysis converged towards biological functions of B cells, in particular the CD40 pathway. When we analyzed peripheral blood transcriptomes in persons with MS, we found a significant dysregulation of MS-associated genes belonging to the EBV interactome in primary progressive MS. This study indicates that the interaction between herpesviruses and predisposing genetic background is of causal significance in MS, and provides a mechanistic explanation for the long-recognized association between EBV and this condition.
Targeting Fe3O4 Au nanoparticles in photoacoustic nuclear magnetic dual-mode imaging
Authors: Protealo David , Smith John 
Published: May 2019

AbstractMulti-mode complementary imaging can improve the accuracy of medical diagnosis. Multi-mode probes are a bridge between various imaging modes, which means that the development of multi-mode, multi-functional nano-probes is very necessary. This paper develops a targeted as a probe for nuclear magnetic and photoacoustic dual-mode imaging, Fe3O4@Au nanoparticles have superparamagnetism and can enhance the nuclear magnetic signal of T2 sequence. The needle has optical absorption properties and can enhance photoacoustic signals. After modifying the surface of Integrin monoclonal antibody, the probe has selective targeting to U87-MG tumor cells. Nuclear magnetic based on Fe3O4@Au nanoparticles /Photoacoustic dual-mode imaging will play a major role in tumor diagnosis.
A flexible simulation toolkit for designing and evaluating ChIP-sequencing experiments
Authors: Zheng An , Lamkin Michael , Qiu Yutong , Ren Kevin , Goren Alon , Gymrek Melissa 
Published: May 2019

AbstractA major challenge in evaluating quantitative ChIP-seq analyses, such as peak calling and differential binding, is a lack of reliable ground truth data. We present Tulip, a toolkit for rapidly simulating ChIP-seq data using statistical models of the experimental steps. Tulip may be used for a range of applications, including power analysis for experimental design, benchmarking of analysis tools, and modeling effects of processes such as replication on ChIP-seq signals.
Sperm-particle interactions and their prospects for charge mapping
Authors: Magdanz Veronika , Gebauer Johannes , Sharan Priyanka , Eltoukhy Samar , Voigt Dagmar , Simmchen Juliane 
Published: May 2019

AbstractIn this article, we demonstrate a procedure to investigate sperm charge distribution by electrostatic sperm-particle interactions. We fabricated and investigated differently charged particles and their attachment distribution on the bovine sperm membrane. We observed the sperm-particle attachment sites using bright field and cryo-scanning electron microscopy combined with energy-dispersive X-ray analysis. Our findings suggest that the charge distribution of the sperm membrane is not uniform and although the overall net charge of the sperm cell is negative, positively charged areas are especially found on the sperm heads. We test the newly developed method to investigate the dynamic charge distribution of the sperm cell membrane upon maturation induced by heparin, as a representation of the multitude of changes during the development of a sperm.