bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sinking diatom aggregates provide carbon to drive microscale denitrification in a bulk oxygenated ocean
Authors: Ciccarese Davide , Tantawi Omar , Zhang Irene , Plata Desiree , Babbin Andrew R. 
Published: September 2022

ABSTRACTSinking marine particles drive the biological gravitational pump that naturally sequesters carbon dioxide from the atmosphere. Ubiquitous throughout the ocean, these particles are largely composed of phytoplankton that aggregate together or are repackaged by zooplankton into pellets that sink to the deep. Despite their small size, the compartmentalized nature of these particles promotes intense localized metabolic activity by the bacteria lucky enough to colonize them. Due to their sheer numbers, these microscale interactions can change the chemistry of the bulk ocean and impact global biogeochemical budgets. As soon as phytoplankton-derived particles are exported from the surface ocean, the fate of the carbon depends on the lability and availability of the carbon, the diffusive supply of oxidants from the bulk, and the development of microbial communities throughout the aggregate. Here we show with a model experimental system that aggregates composed of marine diatoms — important primary producers substantially contributing to global carbon export — can support active denitrification even among bulk oxygenated water ill-conducive to anaerobic metabolisms. We further show the primary nitrite maximum could be formed, in part, due to dissimilatory reduction of nitrate and nitrite occurring at anoxic microsites within such particles. Particle-based denitrification and other anaerobic metabolisms can change the global budget of elemental cycles important for life and climate across the oceans.
DepLink: an R Shiny app to systematically link genetic and pharmacologic dependencies of cancer
Authors: Nayak Tapsya , Wang Li-Ju , Ning Michael , Rubannelsonkumar Gabriela , Jin Eric , Zheng Siyuan , Houghton Peter J. , Huang Yufei , Chiu Yu-Chiao , Chen Yidong 
Published: September 2022

AbstractLarge-scale genetic and pharmacologic dependency maps are generated to reveal genetic vulnerabilities and drug sensitivities of cancer. However, user-friendly software is needed to systematically link such maps. Here we present DepLink, an R Shiny server to identify genetic and pharmacologic perturbations that induce similar effects on cell viability or molecular changes. DepLink integrates heterogeneous datasets of genome-wide CRISPR loss-of-function screens, high-throughput pharmacologic screens, and perturbation expression signatures. The datasets are systematically connected by four complementary modules tailored for different query scenarios. In summary, DepLink enables easy navigation, visualization, and linkage of rapidly evolving cancer dependency maps.
Concurrent measurement of perfusion parameters related to small blood and lymphatic vessels in the human brain using dynamic dual-spin-echo perfusion (DDSEP) MRI
Authors: Cao Di , Sun Yuanqi , Su Pan , Pillai Jay J. , Qiao Ye , Lu Hanzhang , Van Zijl Peter C.M. , Knutsson Linda , Hua Jun 
Published: September 2022

AbstractPURPOSEAccumulating evidence from recent studies has indicated the importance of studying the interaction between the microvascular and lymphatic systems in the brain. To date, most imaging methods can only measure blood or lymphatic vessels separately, such as dynamic-susceptibility-contrast (DSC) MRI for blood vessels and DSC MRI in the CSF (cDSC MRI) for lymphatic vessels. An approach that can measure both blood and lymphatic vessels in a single scan will offer the advantages such as halved scan time and contrast dosage. Based on previous works on DSC and cDSC MRI, this study proposes an MRI approach for concurrent measurement of perfusion parameters related to small blood and lymphatic vessels in the brain within one single scan.METHODSBloch simulations were performed to optimize a dual-echo sequence for the measurement of gadolinium(Gd)-induced blood and CSF signal changes using a short and a long echo time, respectively. MRI experiments were performed in healthy subjects to evaluate the dual-echo approach by comparing it with existing separate methods.RESULTSThe proposed method showed consistent results in human brains as previous studies using separate methods. Signal changes from small blood vessels occurred faster than lymphatic vessels after intravenous Gd-injection.CONCLUSIONGd-induced signal changes in blood and CSF can be detected simultaneously in healthy subjects with the proposed sequence. To the best of our knowledge, this may be the first study in which the temporal difference in Gd-induced signal changes from small blood and lymphatic vessels after intravenous Gd-injection was measured in the same human subjects.
Historical Demography and Climate Driven Range Shifts in the Blue-spotted Salamander Under the Climate Change Scenarios
Authors: Perktaş Utku , Elverici Can , Yaylali Özge 
Published: September 2022

AbstractThis study integrates phylogeography with distributional analysis to understand the demographic history and range dynamics of a limited dispersal capacity amphibian species, Blue-spotted Salamander (Ambystoma laterale), under several climate change scenarios. For this we used an ecological niche modeling approach, together with Bayesian based demographic analysis, to develop inferences regarding this species’ demographic history and range dynamics. The current model output was mostly congruent with the present distribution of the Blue-spotted Salamander. However, under both the Last Interglacial and the Last Glacial Maximum bioclimatic conditions, the model predicted a substantially narrower distribution than the present. These predictions showed almost no suitable area in the current distribution range of the species during almost the last 22.000 y before present (ybp). The predictions indicated that the distribution of this species shifted from eastern coast of northern North America to the southern part of the current distribution range of the species. The Bayesian Skyline Plot analysis, which provided good resolution of the effective population size changes over the Blue-spotted Salamander history, was mostly congruent with ecological niche modeling predictions for this species. This study provides the first investigation of the Blue-spotted Salamander’s late-Quaternary history based on ecological niche modeling and Bayesian-based demographic analysis. In terms of the main result of this study, we found that the species’ present genetic structure has been substantially affected by past climate changes, and this species has reached current distribution range almost from nothing since the Last Glacial Maximum.
A computational understanding of zoomorphic perception in the human brain
Authors: Duyck Stefanie , Bracci Stefania , de Beeck Hans Op 
Published: September 2022

AbstractIt is common to find objects that resemble animals on purpose (e.g., toys). While the perception of such objects as animal-like seems obvious to humans, such “Animal bias” for zoomorphic objects turned out to be a striking discrepancy between the human brain and artificial visual systems known as deep neural networks (DNNs). We provide a computational understanding of the human Animal bias. We successfully induced this bias in DNNs trained explicitly with zoomorphic objects. Alternative training schedules, focusing on previously identified differences between the brain and DNNs, failed to cause an Animal bias. Specifically, we considered the superordinate distinction between animate and inanimate classes, the sensitivity for faces and bodies, the bias for shape over texture, and the role of ecologically valid categories. These findings provide computational support that the Animal bias for zoomorphic objects is a unique property of human perception yet can be explained by human learning history.
Molecular genetics of GLUT1DS Italian pediatric cohort: 10 novel related-disease variants and structural analysis
Authors: Mauri Alessia , Duse Alessandra , Palm Giacomo , Previtali Roberto , Bova Stefania Maria , Olivotto Sara , Benedetti Sara , Coscia Francesca , Veggiotti Pierangelo , Cereda Cristina 
Published: September 2022

AbstractGLUT1 deficiency syndrome (GLUT1DS1; OMIM #606777) is a rare genetic metabolic disease, characterized by infantile-onset epileptic encephalopathy, global developmental delay, progressive microcephaly and movement disorders (e.g. spasticity and dystonia). It is caused by heterozygous mutations in the SLC2A1 gene, which encodes the GLUT1 protein, a glucose transporter across the blood-brain barrier (BBB). Most commonly these variants arise de novo resulting in sporadic cases, although several familial cases with AD inheritance pattern have been described.Twenty-seven Italian pediatric patients clinically suspect of GLUT1DS from both sporadic and familial cases have been enrolled.We detected by trios sequencing analysis 25 different variants causing GLUT1DS. Of these, 40% of the identified variants (10 out of 25) had never been reported before, including missense, frameshift and splice site variants. Their X-ray structure analyses strongly suggested the potential pathogenic effects of these novel disease-related mutations, broadening the genotypic spectrum heterogeneity found in the SLC2A1 gene. Moreover, 24% is located in a vulnerable region of the GLUT1 protein that involves transmembrane 4 and 5 helices encoded by exon 4, confirming a mutational hotspot in the SLC2A1 gene. Lastly, we investigated possible correlations between mutation type and clinical and biochemical data observed in our GLUT1DS cohort, revealing that splice site and frameshift variants are related to a more severe phenotype and low CSF parameters.Author summaryWe investigated the molecular data of 27 pediatric patients clinically suspect of GLUT1 deficiency syndrome. By performing trios sequencing analysis, we highlighted ten novel disease-related variants, and their X-ray structure analyses, suggesting the pathogenic effects of these identified mutations. Moreover, the wide clinical and genetic heterogeneity observed in our cohort allowed possible correlations between mutation type and clinical and biochemical data. This analysis enabled to delineate that splice site and frameshift variants are related to a more severe phenotype and low CSF/glucose values. Further clinical and genetic/epigenetics studies could clearly the high phenotypic variability observed in these patients.
Tumour growth: Bayesian parameter calibration of a multiphase porous media model based on in vitro observations of Neuroblastoma spheroid growth in a hydrogel microenvironment
Authors: Hervas-Raluy Silvia , Wirthl Barbara , Guerrero Pedro E. , Rei Gil Robalo , Nitzler Jonas , Coronado Esther , De Mora Sainz Jaime Font , Schrefler Bernhard A. , Gomez-Benito Maria Jose , García-Aznar Jose Manuel , Wall Wolfgang A. 
Published: September 2022

AbstractTo unravel processes that lead to the growth of solid tumours, it is necessary to link knowledge of cancer biology with the physical properties of the tumour and its interaction with the surrounding microenvironment. Our understanding of the underlying mechanisms is however still imprecise. We therefore developed computational physics-based models, which incorporate the interaction of the tumour with its surroundings based on the theory of porous media. However, the experimental validation of such models represents a challenge to its clinical use as a prognostic tool. This study combines a physics-based model with in vitro experiments based on microfluidic devices used to mimic a 3D tumour microenvironment. By conducting a global sensitivity analysis, we identify the most influential input parameters and infer their posterior distribution based on Bayesian calibration. The resulting probability density is in agreement with the scattering of the experimental data and thus validates the modelling approach. Using the proposed workflow, we demonstrate that we can indirectly characterise the mechanical properties of neuroblastoma spheroids that cannot feasibly be measured experimentally.
Ultrastructure of synaptic connectivity within sub-regions of the SCN revealed by genetically encoded EM tag and SBEM
Authors: Calligaro Hugo , Shoghi Azarin , Chen Xinyue , Kim Keun-Young , Liu Yu Hsin , Khov Brian , Finander Benjamin , Le Hiep , Ellisman Mark H. , Panda Satchidananda 
Published: September 2022

AbstractThe suprachiasmatic nucleus (SCN) in the hypothalamus of the vertebrate brain is the central pacemaker regulating circadian rhythmicity throughout the body. The SCN receives photic information through melanopsin-expressing retinal ganglion cells (mRGC) to synchronize the body with environmental light cycles. Determining how these inputs fit into the network of synaptic connections on and between SCN neurons is key to impelling our understanding of the regulation of the circadian clock by light and unraveling the relevant local circuits within the SCN. To map these connections, we used a newly-developed Cre-dependant electron microscopy reporter, APEX2, to label mitochondria of mRGC axons, and serial blockface scanning electron microscopy to resolve the fine structure of mRGC in 3D volumes of the SCN. The maps thus created provide a first draft of the patterns of connectomic organization of SCN in the core and the shell, composed of different neuronal subtypes, and here shown to differ with regard to the patterning of their mRGC input as the shell receives denser mRGCs synaptic inputs compared to the core. This challenges the presently held view that photic information coming directly from the retina is mainly integrated by the core region of the SCN.
Novel phosphorylation of Rab29 that regulates its localization and lysosomal stress response in concert with LRRK2
Authors: Komori Tadayuki , Kuwahara Tomoki , Fujimoto Tetta , Sakurai Maria , Iwatsubo Takeshi 
Published: September 2022

AbstractRab proteins are small GTPases that regulate a myriad of intracellular membrane trafficking events. Rab29 is one of the Rab proteins phosphorylated by leucine-rich repeat kinase 2 (LRRK2), a Parkinson’s disease-associated kinase. Recent studies suggest that Rab29 regulates LRRK2, whereas the mechanism by which Rab29 is regulated remained unclear. Here we report a novel phosphorylation in Rab29 that is not mediated by LRRK2 and occurs under lysosomal overload stress. Mass spectrometry analysis identified the phosphorylation site of Rab29 as Ser185, and cellular expression studies of phosphomimetic mutants of Rab29 at Ser185 unveiled the involvement of this phosphorylation in counteracting lysosomal enlargement. PKCα was deemed to be responsible for this phosphorylation and control the lysosomal localization of Rab29 in concert with LRRK2. These results implicate PKCα in the lysosomal stress response pathway comprised of Rab29 and LRRK2, and further underscore the importance of this pathway in the mechanisms underlying lysosomal homeostasis.
Extracting extended vocal units from two neighborhoods in the embedding plane
Authors: Lorenz Corinna , Hao Xinyu , Tomka Tomas , Rüttimann Linus , Hahnloser Richard H.R. 
Published: September 2022

AbstractAnnotating and proofreading data sets of complex natural behaviors are tedious tasks because instances of a given behavior need to be correctly segmented from background noise and must be classified with minimal false positive error rate. Low-dimensional embeddings have proven very useful for this task because they provide a visually appealing overview of a data set in which relevant clusters appear spontaneously. However, low-dimensional embeddings introduce errors because they fail to preserve high dimensional distances; and embeddings represent only objects of fixed dimensionality, which conflicts with natural objects such as vocalizations that have variable dimensions stemming from their variable durations. To mitigate these issues, we introduce a semi-supervised method for simultaneous segmentation and clustering of vocalizations. We define vocal units of a given type in terms of two density-based regions in low-dimensional embedding space, one associated with onsets and the other with offsets. We demonstrate our approach on the task of clustering adult zebra finch vocalizations embedded into the 2d plane with UMAP. We show that two-neighborhood (2N) extraction allows the identification of short and long vocal renditions from continuous data streams without initially committing to a particular segmentation of the data. Also, 2N vocal extraction achieves much lower false positive error rate than approaches based on a single defining region.
Deleterious effects of thermal and water stresses on life history and physiology: a case study on woodlouse
Authors: Depeux Charlotte , Branger Angèle , Moulignier Théo , Moreau Jérôme , Lemaître Jean-François , Dechaume-Moncharmont François-Xavier , Laverre Tiffany , Pauhlac Hélène , Gaillard Jean-Michel , Beltran-Bech Sophie 
Published: September 2022

AbstractWe tested independently the influences of increasing temperature and decreasing moisture on life history and physiological traits in the arthropodArmadillidium vulgare. Both increasing temperature and decreasing moisture led reproductive success to decrease. While the density of immune cells decreased and the β-galactosidase activity increased with increasing temperature and decreasing moisture, which suggests a negative impact of these stressors on individual performance, increased temperature and decreased moisture affected differently the other biomarkers conjuring different underlying mechanisms depending on the stress applied. Our findings demonstrate overall a negative impact of high temperature and low moisture on woodlouse welfare. Changing temperature or moisture had slightly different effects, illustrating the need to test further the respective role of each of these key components of climate change on organisms to predict more reliably the future of our ecosystems.
Targeting neuroinflammation by pharmacologic down-regulation of inflammatory pathways is neuroprotective in protein misfolding disorders
Authors: Risen Sydney J. , Boland Sean W. , Sharma Sadhana , Weisman Grace M. , Shirley Payton M. , Latham Amanda S. , Hay Arielle J.D. , Gilberto Vincenzo S. , Hines Amelia D. , Brindley Stephen , Brown Jared M. , McGrath Stephanie , Chatterjee Anushree , Nagpal Prashant , Moreno Julie A. 
Published: September 2022

AbstractNeuroinflammation plays a crucial role in the development of neurodegenerative protein misfolding disorders. This category of progressive diseases includes, but is not limited to, Alzheimer’s disease, Parkinson’s disease, and prion diseases. Shared pathogenesis involves the accumulation of misfolded proteins, chronic neuroinflammation, and synaptic dysfunction, ultimately leading to irreversible neuronal loss, measurable cognitive deficits, and death. Presently, there are little to no effective treatments to halt the advancement of neurodegenerative diseases. We hypothesized directly targeting neuroinflammation by downregulating the transcription factor, NF-κB and the inflammasome protein, NLRP3, with the brain-penetrant, non-toxic, SB_NI_112, would be neuroprotective. To achieve this, we used a cocktail of RNA targeting therapeutics (SB_NI_112) shown to be brain-penetrant, non-toxic, and targeting both NF-|B and NLRP3. We utilized a mouse-adapted prion strain as a model for neurodegenerative diseases to assess aggregation of misfolded proteins, glial inflammation, neuronal loss, cognitive deficits, and lifespan. Prion-diseased mice were treated either intraperitoneally or intranasally with SB_NI_112. Behavioral and cognitive deficits were significantly protected by this combination of NF-κB and NLRP3 down-regulators. Treatment reduced glial inflammation, protected against neuronal loss, prevented spongiotic change, rescued cognitive deficits, and significantly lengthened lifespan of prion-diseased mice. We have identified a non-toxic, systemic pharmacologic that down-regulates NF-|B and NLRP3, prevents neuronal death and slows the progression of neurodegenerative disease. Though mouse models do not always predict human patient success, and the study was limited due to sample size and number of dosing methods utilized, these findings serve as a proof of principle for continued translation of the therapeutic SB_NI_112 for prion disease and other neurodegenerative diseases. Based on success in a murine prion model, we will be continual testing SB_NI_112 in a variety of neurodegenerative disease models, including Alzheimer’s Disease and Parkinson’s Disease.
Biological age and brain age in midlife: relationship to multimorbidity and mental health
Authors: Zhang Fengqing , Chang Hansoo , Schaefer Stacey M. , Gou Jiangtao 
Published: September 2022

AbstractMultimorbidity, co-occurrence of two or more chronic conditions, is one of the top priorities in global health research and has emerged as the gold standard approach to study disease accumulation. As aging underlies the development of many chronic conditions, surrogate aging biomarkers are not disease-specific and capture health at the whole person level, having the potential to improve our understanding of multimorbidity. Biological age has been examined in recent years as a surrogate biomarker to capture the process of aging. However, relatively few studies have investigated the relationship between biological age and multimorbidity. More research is needed to quantify biological age using a broad range of biological markers and multimorbidity based on a comprehensive set of chronic conditions. Brain age estimated by neuroimaging data and machine learning models is another surrogate aging biomarker predictive of a wide range of health outcomes. Little is known about the relationship between brain age and multimorbidity. To answer these questions, our study investigates whether elevated biological age and accelerated brain age are associated with an increased risk of multimorbidity using a large dataset from the Midlife in the United States (MIDUS) Refresher study. Ensemble learning is utilized to combine multiple machine learning models to estimate biological age using a comprehensive set of biological markers. Brain age is obtained using convolutional neural networks and neuroimaging data. Our study is the first to examine the relationship between accelerated brain age and multimorbidity and presents the first effort to test whether sex moderates the relationship between these surrogate aging biomarkers and multimorbidity. Furthermore, it is the first attempt to explore how biological age and brain age are related to multimorbidity in mental health. Our findings hold the potential to advance the understanding of the accumulation of physical and mental health conditions, which may contribute to new strategies to improve the treatment of multimorbidity and detection of at-risk individuals.