bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the effects of deep brain stimulation using a reduced coupled oscillator model
Authors: Weerasinghe Gihan , Duchet Benoit , Cagnan Hayriye , Brown Peter , Bick Christian , Bogacz Rafal 
Published: October 2018

AbstractDeep brain stimulation (DBS) is known to be an effective treatment for a variety of neurological disorders, including Parkinson’s disease and essential tremor (ET). At present, it involves administering a train of pulses with constant frequency via electrodes implanted into the brain. New ‘closed-loop’ approaches involve delivering stimulation according to the ongoing symptoms or brain activity and have the potential to provide improvements in terms of efficiency, efficacy and reduction of side effects. The success of closed-loop DBS depends on being able to devise a stimulation strategy that minimizes oscillations in neural activity associated with symptoms of motor disorders. A useful stepping stone towards this is to construct a mathematical model, which can describe how the brain oscillations should change when stimulation is applied at a particular state of the system. Our work focuses on the use of coupled oscillators to represent neurons in areas generating pathological oscillations. Using a reduced form of the Kuramoto model, we analyse how a patient should respond to stimulation when neural oscillations have a given phase and amplitude. We predict that, provided certain conditions are satisfied, the best stimulation strategy should be phase specific but also that stimulation should have a greater effect if applied when the amplitude of brain oscillations is lower. We compare this surprising prediction with data obtained from ET patients. In light of our predictions, we also propose a new hybrid strategy which effectively combines two of the strategies found in the literature, namely phase-locked and adaptive DBS.Author summaryDeep brain stimulation (DBS) involves delivering electrical impulses to target sites within the brain and is a proven therapy for a variety of neurological disorders. Closed loop DBS is a promising new approach where stimulation is applied according to the state of a patient. Crucial to the success of this approach is being able to predict how a patient should respond to stimulation. Our work focusses on DBS as applied to patients with essential tremor (ET). On the basis of a theoretical model, which describes neurons as oscillators that respond to stimulation and have a certain tendency to synchronize, we provide predictions for how a patient should respond when stimulation is applied at a particular phase and amplitude of the ongoing tremor oscillations. Previous experimental studies of closed loop DBS provided stimulation either on the basis of ongoing phase or amplitude of pathological oscillations. Our study suggests how both of these measurements can be used to control stimulation. As part of this work, we also look for evidence for our theories in experimental data and find our predictions to be satisfied in one patient. The insights obtained from this work should lead to a better understanding of how to optimise closed loop DBS strategies.
Characterization of BSN175: A Drug to Treat Prader-Willi Syndrome
Authors: Ackerman Alyson , Lodder Robert A. 
Published: October 2018

AbstractThe purpose of this research is to choose the best analytical method for determining stability of BSN175. This research uses an accelerated stability study to compare the decomposed and stable drug using IR and 1H NMR spectroscopy. The Bootstrap Error-adjusted Single-sample Technique (BEST) was used to compare the effectiveness of these analytical methods and choose the best option for determining stability.
Polygenic prediction of breast cancer: comparison of genetic predictors and implications for screening
Authors: Läll Kristi , Lepamets Maarja , Palover Marili , Esko Tõnu , Metspalu Andres , Tõnisson Neeme , Padrik Peeter , Mägi Reedik , Fischer Krista 
Published: October 2018

AbstractBackgroundPublished genetic risk scores for breast cancer (BC) so far have been based on a relatively small number of markers and are not necessarily using the full potential of large-scale Genome-Wide Association Studies. This study aims to identify an efficient polygenic predictor for BC based on best available evidence and to assess its potential for personalized risk prediction and screening strategies.MethodsFour different genetic risk scores (two already published and two newly developed) and their combinations (metaGRS) are compared in the subsets of two population-based biobank cohorts: the UK Biobank (UKBB, 3157 BC cases, 43,827 controls) and Estonian Biobank (EstBB, 317 prevalent and 308 incident BC cases in 32,557 women). In addition, correlations between different genetic risk scores and their associations with BC risk factors are studied in both cohorts.ResultsThe metaGRS that combines two genetic risk scores (metaGRS2 - based on 75 and 898 Single Nucleotide Polymorphisms, respectively) has the strongest association with prevalent BC status in both cohorts. One standard deviation difference in the metaGRS2 corresponds to an Odds Ratio = 1.6 (95% CI 1.54 to 1.66, p = 9.7*10-135) in the UK Biobank and accounting for family history marginally attenuates the effect (Odds Ratio = 1.58, 95% CI 1.53 to 1.64, p = 9.1*10-129). In the EstBB cohort, the hazard ratio of incident BC for the women in the top 5% of the metaGRS2 compared to women in the lowest 50% is 4.2 (95% CI 2.8 to 6.2, p = 8.1*10-13). The different GRSs are only moderately correlated with each other and are associated with different known predictors of BC. The classification of genetic risk for the same individual may vary considerably depending on the chosen GRS.ConclusionsWe have shown that metaGRS2 that combines on the effects of more than 900 SNPs provides best predictive ability for breast cancer in two different population-based cohorts. The strength of the effect of metaGRS2 indicates that the GRS could potentially be used to develop more efficient strategies for breast cancer screening for genotyped women.
Directing voluntary temporal attention increases fixational stability
Authors: Denison Rachel N. , Yuval-Greenberg Shlomit , Carrasco Marisa 
Published: October 2018

AbstractOur visual input is constantly changing, but not all moments are equally relevant. Temporal attention, the prioritization of visual information at specific points in time, increases perceptual sensitivity at behaviorally relevant times. The dynamic processes underlying this increase are unclear. During fixation, humans make small eye movements called microsaccades, and inhibiting microsaccades improves perception of brief stimuli. Here we asked whether temporal attention changes the pattern of microsaccades in anticipation of brief stimuli. Human observers (female and male) judged brief stimuli presented within a short sequence. They were given either an informative precue to attend to one of the stimuli, which was likely to be probed, or an uninformative (neutral) precue. We found strong microsaccadic inhibition before the stimulus sequence, likely due to its predictable onset. Critically, this anticipatory inhibition was stronger when the first target in the sequence (T1) was precued (task-relevant) than when the precue was uninformative. Moreover, the timing of the last microsaccade before T1 and the first microsaccade after T1 shifted, such that both occurred earlier when T1 was precued than when the precue was uninformative. Finally, the timing of the nearest pre- and post-T1 microsaccades affected task performance. Directing voluntary temporal attention therefore impacts microsaccades, helping to stabilize fixation at the most relevant moments, over and above the effect of predictability. Just as saccading to a relevant stimulus can be an overt correlate of the allocation of spatial attention, precisely timed gaze stabilization can be an overt correlate of the allocation of temporal attention.Significance statementWe pay attention at moments in time when a relevant event is likely to occur. Such temporal attention improves our visual perception, but how it does so is not well understood. Here we discovered a new behavioral correlate of voluntary, or goal-directed, temporal attention. We found that the pattern of small fixational eye movements called microsaccades changes around behaviorally relevant moments in a way that stabilizes the position of the eyes. Microsaccades during a brief visual stimulus can impair perception of that stimulus. Therefore, such fixation stabilization may contribute to the improvement of visual perception at attended times. This link suggests that in addition to cortical areas, subcortical areas mediating eye movements may be recruited with temporal attention.
Laws for Glia Organization Conserved Across Mammals
Authors: Pinto-Duarte Antonio , Bogue Katharine , Sejnowski Terrence J. , Srinivasan Shyam 
Published: October 2018

AbstractThe organizational principles of glia remain largely unknown despite their vital role in nervous system function. Previous work has shown that the number of glia per unit volume of neocortex is constant across mammalian species. We hypothesize that the conservation of glia volume density within brain regions might be a governing principle of organization across species. To test this hypothesis, we used stereology, light microscopy, and data available in the literature to examine five brain regions: the cerebral cortex and four brain regions that differ from the cerebral cortex and each other - the anterior piriform cortex, the posterior piriform cortex, the entorhinal cortex, and the cerebellum. We discovered two orderly relationships: First, glia volume density within a brain region was constant across species, including humans, although it significantly differed between regions, suggesting that glia density might constitute a region-specific marker. Second, the ratio of glia to neuron increased with brain volume according to a ¼ power law in the primate frontal cortex and the neocortex, the mammalian paleocortex, and the cerebellum. These relationships show that the development of glia and neurons are coupled, and suggest that what a neural circuit computes depends as much on its glial components as on its neurons.Main PointsThe volume density of glia (i.e., number of glia per unit volume) within a brain region is con-served across mammalian species including humans.The ratio of glia to neuron increases with bigger brains.The volume density of glia is significantly different across functionally and architecturally dif-ferent brain regions and could function as a region-specific marker.Glia obey scaling constraints that are different from scaling constraints for neurons.
Complement 3 signaling is necessary for the developmental refinement of olfactory bulb circuitry
Authors: Lehmann Katherine S. , Wood Alynda , Cummings Diana , Bai Li , Stevens Beth , Belluscio Leonardo 
Published: October 2018

AbstractThe olfactory system depends upon organizational maps that are developmentally refined and maintained, however the cellular and molecular mechanisms that underlie these processes are unknown. Studies have shown that microglia and complement molecules are important for the developmental refinement of circuitry within the visual system, thus we asked whether they played a similar role in the olfactory system through the formation of the olfactory bulb (OB) maps, the glomerular and intrabulbar maps. Our findings revealed that microglia in mature animals engulf olfactory sensory neuron (OSN) axons and the synaptic terminals of tufted cells in the glomerular and intrabulbar maps respectively, suggesting microglia could anatomically shape the mature OB circuitry. To determine the mechanisms underlying this axonal pruning activity we used complement 3 (C3) and complement receptor 3 (CR3) knockout mice to investigate if C3 signaling was necessary for precise OB map development. Our results demonstrate that glomerular and intrabulbar map disorganization as typically present in early postnatal mice persists into adulthood when C3 signaling is disrupted. These data clearly establish the C3/CR3 pathway as necessary for the proper developmental refinement of both olfactory maps. We further present the olfactory system as a unique platform to study the role of glia in the development and adult refinement of regenerating circuits.
The genome of the plague-resistant great gerbil reveals species-specific duplication of an MHCII gene
Authors: Nilsson Pernille , Solbakken Monica H. , Schmid Boris V. , Orr Russell J. S. , Lv Ruichen , Cui Yujun , Song Yajun , Zhang Yujiang , Stenseth Nils Chr. , Yang Ruifu , Jakobsen Kjetill S. , Easterday W. Ryan , Jentoft Sissel 
Published: October 2018

AbstractThe great gerbil (Rhombomys opimus) is a social rodent living in permanent, complex burrow systems distributed throughout Central Asia, where it serves as the main host of several important vector-borne infectious diseases and is defined as a key reservoir species for plague (Yersinia pestis). Studies from the wild have shown that the great gerbil is largely resistant to plague but the genetic basis for resistance is yet to be determined. Here, we present a highly contiguous annotated genome assembly of great gerbil, covering over 96 % of the estimated 2.47 Gb genome. Comparative genomic analyses focusing on the immune gene repertoire, reveal shared gene losses withinTLRgene families (i.e.TLR8, TLR10and all members ofTLR11-subfamily) for the Gerbillinae lineage, accompanied with signs of diversifying selection ofTLR7andTLR9. Most notably, we find a great gerbil-specific duplication of theMHCII DRBlocus.In silicoanalyses suggest that the duplicated gene provides high peptide binding affinity forYersiniaeepitopes. The great gerbil genome provides new insights into the genomic landscape that confers immunological resistance towards plague. The high affinity forYersiniaepitopes could be key in our understanding of the high resistance in great gerbils, putatively conferring a faster initiation of the adaptive immune response leading to survival of the infection. Our study demonstrates the power of studying zoonosis in natural hosts through the generation of a genome resource for further comparative and experimental work on plague survival and evolution of host-pathogen interactions.
Why would parthenogenetic females systematically produce males who never transmit their genes to females?
Authors: Grosmaire Manon , Launay Caroline , Siegwald Marion , Félix Marie-Anne , Gouyon Pierre-Henri , Delattre Marie 
Published: October 2018

SummaryIn pseudogamous species, females use the sperm of males from another species to activate their oocytes and produce females, without using the sperm DNA. Here we report a novel reproductive strategy found in the pseudogamous nematode Mesorhabditis belari, which produces its own males at low frequency. We find that the 8% of M. belari males are necessary to fertilize all oocytes but pass on their genes only to males, and never to females. Thus, the production of males has no impact on the genetic diversity of females. Using game theory, we show that the production of males at low frequency constitutes an efficient strategy only if sons are more likely to mate with their sisters. We validate this prediction experimentally by revealing a mating preference between siblings. We uncover the remarkable reproductive strategy of parthenogenetic females that pay the cost of producing males while males do not spread their genes.
Trem2promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions
Authors: Liu Wenfei , Taso Orjona , Wang Rui , Bayram Sevinc , Garcia-Reitboeck Pablo , Mallach Anna , Andrews William D. , Piers Thomas M. , Graham Andrew C. , Botia Juan A. , Pocock Jennifer M. , Cummings Damian M. , Hardy John , Edwards Frances A. , Salih Dervis A. 
Published: October 2018

AbstractGenome-wide association studies have reported that, amongst other microglial genes, variants inTREM2can profoundly increase the incidence of developing Alzheimer’s disease (AD). We have investigated the role of TREM2 in primary microglial cultures from wild type mice by using siRNA to decreaseTrem2expression, and in parallel from knock-in mice heterozygous or homozygous for theTrem2R47H AD risk variant. The prevailing phenotype ofTrem2R47H knock-in mice was decreased expression levels ofTrem2in microglia, which resulted in decreased density of microglia in the hippocampus. Overall, primary microglia with reducedTrem2expression, either by siRNA or from the R47H knock-in mice, displayed a similar phenotype. Comparison of the effects of decreasedTrem2expression under conditions of LPS pro-inflammatory or IL-4 anti-inflammatory stimulation revealed the importance ofTrem2in driving a number of the genes up-regulated in the anti-inflammatory phenotype. RNA-seq analysis showed that IL-4 induced the expression of a programme of genes includingArg1andAp1b1in microglia, which showed an attenuated response to IL-4 whenTrem2expression was decreased. Genes showing a similar expression profile toArg1were enriched for STAT6 transcription factor recognition elements in their promoter, andTrem2knockdown decreased levels of the transcription factor STAT6. LPS-induced pro-inflammatory stimulation suppressedTrem2expression, thus preventing TREM2’s anti-inflammatory drive. Given that anti-inflammatory signaling is associated with tissue repair, understanding the signaling mechanisms downstream ofTrem2in coordinating the pro- and anti-inflammatory balance of microglia, particularly mediating effects of the IL-4-regulated anti-inflammatory pathway, has important implications for fighting neurodegenerative disease.Graphical abstract
Genetic population variation and phylogeny ofSinomenium acutum(Menispermaceae) in subtropical China through chloroplast marker
Authors: He Ying , Guo Chun , Zeng Xiyao , Yang Hua , Xiong Xingyao , Qiu Ping 
Published: October 2018

AbstractSinomenium acutum(Menispermaceae) is a traditional Chinese medicine. In recent years, extensive harvesting for medicinal purposes has resulted in a sharp decline in its population. Genetic information is crucial for the proper exploitation and conservation ofSinomenium acutum, but little is known about it at present. In this study, we analyzed 77 samples from 4 populations using four non-coding regions (atpI-atpH,trnQ-5’rps16,trnH-psbA, andtrnL-trnF) of chloroplast DNA and 14 haplotypes (from C1 to C14) were identified. C1 and C3 were common haplotypes, which were shared by all populations, and C3 was an ancestral haplotype, the rest were rare haplotypes. Obvious phylogeographic structure was not existed inferred byGST/NSTtest. Mismatch distribution, Tajima’s D and Fu’s FStests failed to support a rapid demographic expansion inSinomenium acutum. AMOVA highlighted that the high level of genetic differentiation within population. Low genetic variation among populations illustrated gene flow was not restricted. Genetic diversity analyses demonstrated that the populations of Xuefeng, Dalou, and Daba Mountains were possible refugia localities ofSinomenium acutum. Based on this study, we proposed a preliminary protection strategy for it that C1, C3, C11 and C12 must be collected. These results offer an valuable and useful information for this species of population genetic study as well as further conservation.
Prokaryotic community shifts during soil formation on sands in the tundra zone
Authors: Zhelezova Alena , Chernov Timofey , Tkhakakhova Azida , Xenofontova Natalya , Semenov Mikhail , Kutovaya Olga 
Published: October 2018

AbstractA chronosequence approach,i.e., a comparison of spatially distinct plots with different stages of succession, is commonly used for studying microbial community dynamics during paedogenesis. The successional traits of prokaryotic communities following sand fixation processes have previously been characterized for arid and semi-arid regions, but they have not been considered for the tundra zone, where the environmental conditions are unfavourable for the establishment of complicated biocoenoses. In this research, we characterized the prokaryotic diversity and abundance of microbial genes found in a typical tundra and wooded tundra along a gradient of increasing vegetation – unfixed aeolian sand, semi-fixed surfaces with mosses and lichens, and mature soil under fully developed plant cover. Microbial communities from typical tundra and wooded tundra plots at three stages of sand fixation were compared using quantitative polymerase chain reaction (qPCR) and high-throughput sequencing of 16S rRNA gene libraries. The abundances of ribosomal genes increased gradually in both chronosequences, and a similar trend was observed for the functional genes related to the nitrogen cycle (nifH, bacterialamoA, nirKandnirS). The relative abundance ofPlanctomycetesincreased, while those ofThaumarchaeota, CyanobacteriaandChloroflexidecreased from unfixed sands to mature soils. According to β-diversity analysis, prokaryotic communities of unfixed sands were more heterogeneous compared to those of mature soils. Despite the differences in the plant cover of the two mature soils, the structural compositions of the prokaryotic communities were shaped in the same way.
Taking a deeper look: Quantifying the differences in fish assemblages between shallow and mesophotic temperate rocky reefs
Authors: Williams Joel , Jordan Alan , Harasti David , Davies Peter , Ingleton Tim 
Published: October 2018

AbstractThe spatial distribution of a species assemblage is often determined by habitat and climate. In the marine environment, depth can become an important factor as degrading light leads to changes in the biological habitat structure. To date, much of the focus of ecological fish research has been based on reefs in less than 40 m with little research on the ecological role of mesophotic reefs. We deployed baited remote underwater stereo video systems (stereo-BRUVS) on temperate reefs in two depth categories: shallow (20-40m) and mesophotic (80-120m), off Port Stephens, Australia. Sites were selected using data collected by swath acoustic sounder to ensure stereo-BRUVS were deployed on reef. The sounder also provided rugosity, slope and relief data for each stereo-BRUVS deployment. Multivariate analysis indicates that there are significant differences in the fish assemblages between shallow and mesophotic reefs, primarily driven by Ophthalmolepis lineolatus and Notolabrus gymnogenis only occurring on shallow reefs and schooling species of fish that were unique to each depth category: Atypichthys strigatus on shallow reefs and Centroberyx affinis on mesophotic reefs. While shallow reefs had a greater species richness and abundance of fish when compared to mesophotic reefs, mesophotic reefs hosted the same species richness of fishery targeted species. Chrysophrys auratus (pink snapper) and Nemodactylus douglassii (grey morwong) are two highly targeted species in this region. While C. auratus was numerically more abundant on shallow reefs, mesophotic reefs provide habitat for larger fish. In comparison, N. douglassii were evenly distributed across all sites sampled. Generalized linear models revealed that depth and habitat type provided the most parsimonious model for predicting the distribution of C. auratus, while habitat type alone best predicted the distribution of N. douglassii. These results demonstrate the importance of mesophotic reefs to fishery targeted species and therefore have implications for informing the management of these fishery resources on shelf rocky reefs.