bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trade-offs of managing Arctic predator harvest instability in fluctuating oceans
Authors: Goto Daisuke , Filin Anatoly A. , Howell Daniel , Bogstad Bjarte , Kovalev Yury , Gjøsæter Harald 
Published: June 2020

AbstractSustainable human exploitation of marine living resources stems from a delicate balance between short-term yield stability and long-term population persistence to achieve socioeconomic and conservation goals. However, imperfect knowledge of how oscillations in ecosystem processes regulate fluctuations in exploited populations can obscure the risk of missing management targets. We illustrate how the harvest policy to suppress short-term yield fluctuation inadvertently disrupts population cycles and yield stability of exploited, long-lived predators under stochastically fluctuating environmental forces (food availability and regional climate) using Northeast Arctic (NEA) cod (Gadus morhua, an apex predatory fish) as a case study. We use a stochastic, empirically parameterized multispecies model to simulate NEA cod population dynamics through life-history processes; Barents Sea capelin (Mallotus villosus, a pelagic forage fish) modulates cod productivity through density-dependent cannibalism–predation dynamics, whereas sea temperature regulates cod consumption, growth, and recruitment. We first test how capelin and sea temperature fluctuations regulate patterns in cod yield fluctuation and then quantitatively assess how fishing pattern designed to limit yield between-year variance (within 50–5%) perturbs cod population–catch dynamics. Simulations suggest that capelin and temperature interactively contribute to shifting cyclic patterns in cod yield fluctuation primarily through cod cannibalism–predation dynamics. Wavelet analyses further show that muffling yield variance (30 % or less) reshapes the cyclicity (shorter period and greater amplitude) of cod population size and demography, thereby becoming progressively unsynchronized with fishing pressure. Our work reveals unintended consequences of managing transient dynamics of fished populations: the interworking of population cycle destabilized by inadvertently intensifying fishing pressure, amplifying yield fluctuation and, in turn, elevating overharvest risk when not accounting for compounded effects of stochasticity in ecologically connected processes. These policy implications underscore the need for an ecosystem approach to designing ecologically sound management measures to safely harvest shared living resources while achieving socioeconomic security in increasingly more dynamic oceans in the Arctic and elsewhere.
One-shot learning with spiking neural networks
Authors: Scherr Franz , Stöckl Christoph , Maass Wolfgang 
Published: June 2020

AbstractUnderstanding how one-shot learning can be accomplished through synaptic plasticity in neural networks of the brain is a major open problem. We propose that approximations toBPTTin recurrent networks of spiking neurons (RSNNs) such ase-propcannot achieve this because their local synaptic plasticity is gated by learning signals that are rather ad hoc from a biological perspective: Random projections of instantaneously arising losses at the network outputs, analogously as in Broadcast Alignment for feedforward networks. In contrast, synaptic plasticity is gated in the brain by learning signals such as dopamine, which are emitted by specialized brain areas, e.g. VTA. These brain areas have arguably been optimized by evolution to gate synaptic plasticity in such a way that fast learning of survival-relevant tasks is enabled. We found that a corresponding model architecture, where learning signals are emitted by a separate RSNN that is optimized to facilitate fast learning, enables one-shot learning via local synaptic plasticity in RSNNs for large families of learning tasks. The same learning approach also supports fast spike-based learning of posterior probabilities of potential input sources, thereby providing a new basis for probabilistic reasoning in RSNNs. Our new learning approach also solves an open problem in neuromorphic engineering, where on-chip one-shot learning capability is highly desirable for spike-based neuromorphic devices, but could so far not be achieved. Our method can easily be mapped into neuromorphic hardware, and thereby solves this problem.
Biological invasions alter environmental microbiomes: a meta-analysis
Authors: Malacrinò Antonino , Sadowski Victoria A. , Martin Tvisha K. , de Oliveira Nathalia Cavichiolli , Brackett Ian J. , Feller James D. , Harris Kristian J. , Heredia Orlando Combita , Vescio Rosa , Bennett Alison E. 
Published: June 2020

AbstractBiological invasions impact both agricultural and natural systems. The damage can be quantified in terms of both economic loss and reduction of biodiversity. Although the literature is quite rich about the impact of invasive species on plant and animal communities, their impact on environmental microbiomes is underexplored. Here, we re-analyze publicly available data using a common framework to create a global synthesis of the effects of biological invasions on environmental microbial communities. Our findings suggest that non-native species are responsible for the loss of microbial diversity and shifts in the structure of microbial populations. Therefore, the impact of biological invasions on native ecosystems might be more pervasive than previously thought, influencing both macro- and micro-biomes. We also identified gaps in the literature which encourage research on a wider variety of environments and invaders, and the influence of invaders across seasons and geographical ranges.
Exaggerated postnatal surge of orexin and the effects of elimination of excess orexin on blood pressure in spontaneously hypertensive rats in postnatal development
Authors: Barnett Savannah , Dong Ruhong , Briggs Logan , Moushey Alexander , Li Aihua 
Published: June 2020

AbstractIt has been established that an overactive orexin (OX) system is associated with neurogenic hypertension in spontaneously hypertensive rats (SHRs). However, the chronology and mechanism of such association between orexin system and hypertension is unclear. We hypothesized that an aberrant surge of OX neurons in SHRs precedes the aberrant increase of arterial blood pressure (ABP) during postnatal development, which was primarily contributed by the exaggerated postnatal OX neurogenesis. We found that (1) SHRs experienced a greater surge in the number of orexin neurons than normotensive Wistar-Kyoto (WKY) rats before P16, which led to significantly more OX neurons than age-matched controls by P15-16 (3680±219 vs 2407±182, respectively, P=0.002). (2) Exaggerated OX neurogenesis, marked by bromodeoxyuridine (BrdU), was the primary contributor to excessive OX neurons in SHRs during development. (3) In contrast, SHRs and normotensive control rats have similar mean arterial blood pressure (ABP) at P15, and a significantly higher ABP in SHR than WKY emerges at P20 (74.8 ± 2.5 vs 66.9 ± 4.4 mmHg in wakefulness, respectively, P<0.05), a few days following the surge of OX activity. (4) Selectively eliminating excess (∼30%) orexin neurons, via a targeted neurotoxin, in SHRs between P30 and P40 results in a significantly lowered ABP compared to non-lesioned SHRs at P40. We suggest that the postnatal surge of OX neurons, primarily attributed to the exaggerated postnatal OX neurogenesis, may be necessary for the development of higher ABP in SHRs, and modulation of the overactive OX system may have a preventative effect during the pre-hypertensive period.New FindingsWhat is the central question of this study?Excess orexin neurons have been associated with hypertension in spontaneously hypertensive rats, however, the association and mechanism between developing excess orexin neurons and high blood pressure are unknown.What is the main finding and its importance?Using spontaneously hypertensive rats in anatomical and physiological studies, we provided evidence showing that the excess OX neurons, primarily via exaggerated OX neurogenesis, may be necessary in developing a higher ABP in SHRs during development, and modulation of the overactive orexin system may be beneficial in treating hypertension.
Integrated Stress Response Inhibition Provides Sex-Dependent Protection Against Noise-Induced Cochlear Synaptopathy
Authors: Rouse Stephanie L. , Matthews Ian R. , Li Jiang , Sherr Elliott H. , Chan Dylan K. 
Published: June 2020

AbstractNoise-induced hearing loss (NIHL) is a common health concern with significant social, psychological, and cognitive implications. Moderate levels of acoustic overstimulation associated with tinnitus and impaired speech perception cause cochlear synaptopathy, characterized physiologically by reduction in wave I of the suprathreshold auditory brainstem response (ABR) and reduced number of synapses between sensory hair cells and auditory neurons. The unfolded protein response (UPR), an endoplasmic reticulum stress response pathway, has been implicated in the pathogenesis and treatment of NIHL as well as neurodegeneration and synaptic damage in the brain. In this study, we used the small molecule UPR modulator ISRIB (Integrated Stress Response InhiBitor) to treat noise-induced cochlear synaptopathy in a mouse model. Mice pretreated with ISRIB prior to noise-exposure were protected against noise-induced synapse loss. Male, but not female, mice also exhibited ISRIB-mediated protection against noise-induced suprathreshold ABR wave-I amplitude reduction. Female mice had higher baseline wave-I amplitudes but greater sensitivity to noise-induced wave-I reduction. Our results suggest that the UPR is implicated in noise-induced cochlear synaptopathy, and can be targeted for treatment.
SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients
Authors: Walker Susanne N. , Chokkalingam Neethu , Reuschel Emma L. , Purwar Mansi , Xu Ziyang , Gary Ebony N. , Kim Kevin Y. , Schultheis Katherine , Walters Jewell , Ramos Stephanie , Smith Trevor R.F. , Broderick Kate E. , Tebas Pablo , Patel Ami , Weiner David B. , Kulp Daniel W. 
Published: June 2020

AbstractSARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused a global pandemic of COVID-19 resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >8 million people worldwide with >2 million cases in the US (June 17th, 2020). There is an urgent need for vaccines and therapeutics to combat the spread of this coronavirus. Similarly, the development of diagnostic and research tools to determine infection and vaccine efficacy are critically needed. Molecular assays have been developed to determine viral genetic material present in patients. Serological assays have been developed to determine humoral responses to the spike protein or receptor binding domain (RBD). Detection of functional antibodies can be accomplished through neutralization of live SARS-CoV2 virus, but requires significant expertise, an infectible stable cell line, a specialized BioSafety Level 3 (BSL-3) facility. As large numbers of people return from quarantine, it is critical to have rapid diagnostics that can be widely adopted and employed to assess functional antibody levels in the returning workforce. This type of surrogate neutralization diagnostic can also be used to assess humoral immune responses induced in patients from the large number of vaccine and immunotherapy trials currently on-going. Here we describe a rapid serological diagnostic assay for determining antibody receptor blocking and demonstrate the broad utility of the assay by measuring the antibody functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine and using sera from infected patients.
Multiomics Characterization of Potential Therapeutic Vulnerabilities in Low-grade Serous Ovarian Carcinoma
Authors: Shrestha Raunak , Fernandez Marta Llaurado , Dawson Amy , Hoenisch Joshua , Volik Stanislav , Lin Yen-Yi , Anderson Shawn , Kim Hannah , Haegert Anne , Colborne Shane , McConeghy Brian , Bell Robert H. , Brahmbhatt Sonal , DiMattia Gabriel E. , Le Bihan Stephane , Morin Gregg B. , Collins Colin C. , Carey Mark S. 
Published: June 2020

AbstractBackgroundLow-grade serous ovarian carcinoma (LGSOC) is a rare tumor subtype with high case fatality rates. As such, there is a pressing need to develop more effective treatments using newly available preclinical models for therapeutic discovery and drug evaluation. Here, we use a multiomics approach to interrogate a collection of LGSOC patient-derived cell lines to elucidate novel biomarkers and therapeutic vulnerabilities.MethodsFourteen LGSOC cell lines were interrogated using whole exome sequencing, RNA sequencing, and mass spectrometry-based proteomics. Somatic mutation, copy-number aberrations, gene and protein expression were analyzed and integrated using different computational approaches. LGSOC cell line data was compared to publicly available LGSOC tumor data (AACR GENIE cohort), and also used for predictive biomarker identification of MEK inhibitor (MEKi) efficacy. Protein interaction databases were evaluated to identify novel therapeutic targets.ResultsKRASmutations were exclusively found in MEKi-sensitive andNRASmutations mostly in MEKi-resistant cell lines. Analysis of COSMIC mutational signatures revealed distinct patterns of nucleotide substitution mutations in MEKi-sensitive and MEKi-resistant cell lines. Deletions ofCDKN2A/BandMTAPgenes (chromosome 9p21) were much more frequent in cell lines than tumor samples and possibly represent key driver events in the absence of KRAS/NRAS/BRAF mutations. Forin-vitroMEKi efficacy prediction, proteomic data provided better discrimination than gene expression data. Condensin, MCM, and RFC protein complexes were identified as potential treatment targets in MEKi-resistant cell lines.ConclusionsOur LGSOC cell lines are representative models of the most common molecular aberrations found in LGSOC tumors. This study highlights the importance of using proteomic data in multiomics assessment of drug prediction and identification of potential therapeutic targets. CDKN2A/B and MTAP deficiency offer an opportunity to find synthetically lethal candidates for novel treatments. Multiomics approaches are crucial to improving our understanding of the molecular aberrations in LGSOC, establishing effective drug prediction programs and identifying novel therapeutic targets in LGSOC.
The early adolescent brain on music: analysis of functional dynamics reveals engagement of orbitofrontal cortex reward system
Authors: Fasano M. C. , Cabral J. , Stevner A. , Vuust P. , Cantou P. , Brattico E. , Kringelbach M. L. 
Published: June 2020

AbstractMusic listening plays a pivotal role for children and adolescents, yet surprisingly few neuroimaging studies have studied the underlying functional dynamics. We used functional magnetic resonance imaging to scan 17 preadolescents aged 10-11 years old while listening to music. We subsequently tracked the occurrence of functional brain networks over time by using a recent method that detects recurrent BOLD phase-locking states: the Leading Eigenvector Dynamics Analysis (LEiDA). In particular, we compared the probabilities of occurrence and switching profiles of different patterns of BOLD phase-locking between music and no music. Moreover, we used an adapted version of the Barcelona Music Reward Questionnaire (BMRQ) to measure the music reward sensitivity of the participants. Our results showed significantly increased occurrence of a BOLD phase-locking pattern during music listening compared to no music, characterized by a phase-shift in the BOLD signals of the medial orbitofrontal and ventromedial prefrontal cortices – a brain subsystem associated to reward processing – from the rest of the brain. Moreover, we observed a significantly higher probability of switching to this pattern while listening to music. We also found a positive correlation between the individual musical reward sensitivity and the tendency to switch to this reward state during music. Our findings highlight the involvement of a brain subsystem involved in hedonic processing during music listening in the early adolescent brain. These results offer novel insight into the neural underpinnings of musical reward in early adolescence and may help us to understand the importance of music at this delicate age.
“Acute Respiratory Distress and Cytokine Storm in Aged, SARS-CoV-2 Infected African Green Monkeys, but not in Rhesus Macaques”
Authors: Blair Robert V. , Vaccari Monica , Doyle-Meyers Lara A. , Roy Chad J , Russell-Lodrigue Kasi , Fahlberg Marissa , Monjure Chris J. , Beddingfield Brandon , Plante Kenneth S. , Plante Jessica A. , Weaver Scott C. , Qin Xuebin , Midkiff Cecily C. , Lehmicke Gabrielle , Golden Nadia , Threeton Breanna , Penney Toni , Allers Carolina , Barnes Mary B , Pattison Melissa , Datta Prasun K , Maness Nicholas J , Birnbaum Angela , Fischer Tracy , Bohm Rudolf P. , Rappaport Jay 
Published: June 2020

AbstractSARS-CoV-2 induces a wide range of disease severity ranging from asymptomatic infection, to a life-threating illness, particularly in the elderly and persons with comorbid conditions. Among those persons with serious COVID-19 disease, acute respiratory distress syndrome (ARDS) is a common and often fatal presentation. Animal models of SARS-CoV-2 infection that manifest severe disease are needed to investigate the pathogenesis of COVID-19 induced ARDS and evaluate therapeutic strategies. Here we report ARDS in two aged African green monkeys (AGMs) infected with SARS-CoV-2 that demonstrated pathological lesions and disease similar to severe COVID-19 in humans. We also report a comparatively mild COVID-19 phenotype characterized by minor clinical, radiographic and histopathologic changes in the two surviving, aged AGMs and four rhesus macaques (RMs) infected with SARS-CoV-2. We found dramatic increases in circulating cytokines in three of four infected, aged AGMs but not in infected RMs. All of the AGMs showed increased levels of plasma IL-6 compared to baseline, a predictive marker and presumptive therapeutic target in humans infected with SARS-CoV-2 infection. Together, our results show that both RM and AGM are capable of modeling SARS-CoV-2 infection and suggest that aged AGMs may be useful for modeling severe disease manifestations including ARDS.
T4SE-XGB: interpretable sequence-based prediction of type IV secreted effectors using eXtreme gradient boosting algorithm
Authors: Chen Tianhang , Wang Xiangeng , Chu Yanyi , Wei Dong-Qing , Xiong Yi 
Published: June 2020

AbstractType IV secreted effectors (T4SEs) can be translocated into the cytosol of host cells via type IV secretion system (T4SS) and cause diseases. However, experimental approaches to identify T4SEs are time- and resource-consuming, and the existing computational tools based on machine learning techniques have some obvious limitations such as the lack of interpretability in the prediction models. In this study, we proposed a new model, T4SE-XGB, which uses the eXtreme gradient boosting (XGBoost) algorithm for accurate identification of type IV effectors based on optimal features based on protein sequences. After trying 20 different types of features, the best performance was achieved when all features were fed into XGBoost by the 5-fold cross validation in comparison with other machine learning methods. Then, the ReliefF algorithm was adopted to get the optimal feature set on our dataset, which further improved the model performance. T4SE-XGB exhibited highest predictive performance on the independent test set and outperformed other published prediction tools. Furthermore, the SHAP method was used to interpret the contribution of features to model predictions. The identification of key features can contribute to improved understanding of multifactorial contributors to host-pathogen interactions and bacterial pathogenesis. In addition to type IV effector prediction, we believe that the proposed framework can provide instructive guidance for similar studies to construct prediction methods on related biological problems. The data and source code of this study can be freely accessed athttps://github.com/CT001002/T4SE-XGB.
α-Synuclein facilitates endocytosis by elevating the steady-state levels of phosphatidylinositol 4,5-bisphosphate
Authors: Meir Schechter , Merav Atias , Suaad Abd Elhadi , Dana Davidi , Daniel Gitler , Ronit Sharon 
Published: June 2020

Abstractα-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson’s disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for α-Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of α-Syn in these mechanisms is currently unclear. Here we have investigated the role of α-Syn in membrane trafficking through its association with acidic phosphoinositides (PIPs), such as phosphatidylinositol 4,5-bisphosphate (PI4,5P2) and phosphatidylinositol 3,4-bisphosphate (PI3,4P2). Our results show that α-Syn colocalizes with PIP2and the phosphorylated active form of the clathrin adaptor AP2 at clathrin-coated pits. Using endocytosis of transferrin, an indicator of clathrin mediated endocytosis (CME), we find that α-Syn involvement in endocytosis is specifically mediated through PI4,5P2levels. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by α-Syn mutations. In accord with their effects on PI4,5P2levels at the plasma membrane, the PD associated E46K and A53T mutations further enhance SV endocytosis. However, neither A30P mutation, nor Lysine to Glutamic acid substitutions at the KTKEGV repeat domain of α-Syn, that interfere with phospholipid binding, affect SV endocytosis. This study provides evidence for a critical involvement of PIPs in α-Syn-mediated membrane trafficking.Significance Statementα-Synuclein (α-Syn) protein is known for its causative role in Parkinson’s disease. α-Syn is normally involved in mechanisms of membrane trafficking, including endocytosis, exocytosis and synaptic vesicles cycling. However, a certain degree of controversy regarding the exact role of α-Syn in these mechanisms persists. Here we show that α-Syn acts to increase plasma membrane levels PI4,5P2and PI3,4P2to facilitate clathrin mediated and synaptic vesicles endocytosis. Based on the results, we suggest that α-Syn interactions with the acidic phosphoinositides facilitate a shift in their homeostasis to support endocytosis.
Endogenous neural stem cells modulate microglia and protect from demyelination
Authors: Brousse Béatrice , Magalon Karine , Daian Fabrice , Durbec Pascale , Cayre Myriam 
Published: June 2020

SUMMARYIn response to corpus callosum (CC) demyelination, subventricular zone-derived neural progenitors (SVZdNP) are mobilized and generate new myelinating oligodendrocytes. Here, we examine the putative immunomodulatory properties of endogenous SVZdNP during demyelination in the cuprizone model. We observed that SVZdNP density is higher in the lateral and rostral CC regions that show weaker demyelination and is inversely correlated with activated microglia density and pro-inflammatory cytokines levels. Single-cell RNA-sequencing further revealed CC areas with high SVZdNP mobilization are enriched in a microglial cell subpopulation with immunomodulatory signature. We identified ligand/receptor couple MFGE8 (milk fat globule-epidermal growth factor-8)/integrin β3 as a ligand/receptor couple implicated in SVZdNP/microglia dialog. MFGE8 is highly enriched in immature SVZdNP mobilized to the demyelinated CC and promotes myelin debris phagocytosis in vitro. Altogether these results demonstrate that beyond their cell replacement capacity endogenous progenitors display immunomodulatory properties highlighting a new role for endogenous SVZdNP in myelin regeneration.