bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing behavioral sex differences to chemical cues of predation risk while provisioning nestlings in a hole-nesting bird
Authors: Saavedra Irene , Tomás Gustavo , Amo Luisa 
Published: March 2022

AbstractBirds can assess nest predation risk and adjust their parental activity accordingly. Risk taking behavior should be related to investment in reproduction as well as to confidence in parenthood that often differ between sexes. In those cases, sexual differences in risk taking behavior may be expected. For example, in blue tits, females invest more time and energy than males in nest-building, egg laying and incubation. Furthermore, confidence in parenthood is supposed to be higher for females, as extrapair paternity is common in this species. Therefore, the reproductive value of nestlings may be higher for females than for males and the former may assume greater risks to ensure nestling growth and maximize their reproductive success. We examined potential sexual differences in the risk assumed by parents in relation to perceived risk of predation inside the nest cavity, where predation risk perception may be higher. We increased perceived predation risk by adding predator chemical cues inside blue tit (Cyanistes caeruleus) nest-boxes, and we tested whether female and male parents differed in the risk assumed when taking care of nestlings. Females and males did not differ in the risk assumed in response to perceived predation risk. However, females reduced time devoted to nest sanitation activities when predator chemical cues were detected inside the nest-box, likely as an anti-predatory strategy to minimize their own risk of predation. Therefore, these results add to the evidence that birds can detect chemical cues of predators inside the nest cavity and suggest that the behavioral response to an increase in risk of predation perceived through olfactory cues is not sex-dependent in blue tit.
Human bone marrow organoids for disease modelling, discovery and validation of therapeutic targets in hematological malignancies
Authors: Khan Abdullah O. , Colombo Michela , Reyat Jasmeet S. , Wang Guanlin , Rodriguez-Romera Antonio , Wen Wei Xiong , Murphy Lauren , Grygielska Beata , Mahoney Chris , Stone Andrew , Croft Adam , Bassett David , Poologasundarampillai Gowsihan , Roy Anindita , Gooding Sarah , Rayes Julie , Machlus Kellie R , Psaila Bethan 
Published: March 2022

AbstractA lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from iPSCs committed to mesenchymal, endothelial and hematopoietic lineages. These 3-dimensional structures capture key features of human bone marrow - stroma, lumen-forming sinusoidal vessels and myeloid cells including pro-platelet forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGFβ stimulation and engraftment with myelofibrosis but not healthy donor-derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow-like milieu. This enabling technology is likely to accelerate discovery and prioritization of novel targets for bone marrow disorders and blood cancers.Significance StatementWe present a 3D, vascularised human bone marrow organoid that supports growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment, and provides a much-needed, ex vivo tool for prioritization of new therapeutics.
The Influence of Neural Activity and Neural Cytoarchitecture on Cerebrovascular Arborization: A Computational Model
Authors: Kumar Bhadra S , Menon Sarath C , Sriya R G , Chakravarthy V Srinivasa 
Published: March 2022

AbstractNormal functioning of the brain relies on a continual and efficient delivery of energy by a vast network of cerebral blood vessels. The bidirectional coupling between neurons and blood vessels consists of vasodilatory energy demand signals from neurons to blood vessels, and the retrograde flow of energy substrates from the vessels to neurons, which fuel neural firing, growth and other housekeeping activities in the neurons. Recent works indicate that, in addition to the functional coupling observed in the adult brain, the interdependence between the neural and vascular networks begins at the embryonic stage, and continues into subsequent developmental stages. The proposed Vascular Arborization Model (VAM) captures the effect of neural cytoarchitecture and neural activity on vascular arborization.The VAM describes three important stages of vascular tree growth: (i) The prenatal growth phase, where the vascular arborization depends on the cytoarchitecture of neurons and non-neural cells, (ii) the post-natal growth phase during which the further arborization of the vasculature depends on neural activity in addition to neural cytoarchitecture, and (iii) the settling phase, where the fully grown vascular tree repositions its vascular branch points or nodes to ensure minimum path length and wire length. The vasculature growth depicted by VAM captures structural characteristics like vascular volume density, radii, mean distance to proximal neurons in the cortex. VAM-grown vasculature agrees with the experimental observation that the neural densities do not covary with the vascular density along the depth of the cortex but predicts a high correlation between neural areal density and microvascular density when compared over a global scale (across animals and regions).To explore the influence of neural activity on vascular arborization, the VAM was used to grow the vasculature in neonatal rat whisker barrel cortex under two conditions: (i) Control, where the whiskers were intact and (ii) Lesioned, where one row of whiskers was cauterized. The model captures a significant reduction in vascular branch density in lesioned animals compared to control animals, concurring with experimental observation.
Temporal dynamics of competition between statistical learning and episodic memory in intracranial recordings of human visual cortex
Authors: Sherman Brynn E. , Graves Kathryn N. , Huberdeau David M. , Quraishi Imran H. , Damisah Eyiyemisi C. , Turk-Browne Nicholas B. 
Published: March 2022

AbstractThe function of long-term memory is not just to reminisce about the past, but also to make predictions that help us behave appropriately and efficiently in the future. This predictive function of memory provides a new perspective on the classic question from memory research of why we remember some things but not others. If prediction is a key outcome of memory, then the extent to which an item generates a prediction signifies that this information already exists in memory and need not be encoded. We tested this principle using human intracranial EEG as a time-resolved method to quantify prediction in visual cortex during a statistical learning task and link the strength of these predictions to subsequent episodic memory behavior. Epilepsy patients of both sexes viewed rapid streams of scenes, some of which contained regularities that allowed the category of the next scene to be predicted. We verified that statistical learning occurred using neural frequency tagging and measured category prediction with multivariate pattern analysis. Although neural prediction was robust overall, this was driven entirely by items that were subsequently forgotten. Such interference provides a mechanism by which prediction can regulate memory formation to prioritize encoding of information that could help learn new predictive relationships.Significance StatementWhen faced with a new experience, we are rarely at a loss for what to do. Rather, because many aspects of the world are stable over time, we rely upon past experiences to generate expectations that guide behavior. Here we show that these expectations during a new experience come at the expense of memory for that experience. From intracranial recordings of visual cortex, we decoded what humans expected to see next in a series of photographs based on patterns of neural activity. Photographs that generated strong neural expectations were more likely to be forgotten in a later behavioral memory test. Prioritizing the storage of experiences that currently lead to weak expectations could help improve these expectations in future encounters.
ANTARCTIC FUNGI: A BIO-SOURCE ALTERNATIVE TO PRODUCE POLYUNSATURATED FATTY ACIDS (PUFAs)
Authors: De Rossi Patrizia , Ambrico Alfredo , Del Fiore Antonella , Trupo Mario , Blasi Luciano , Beccaccioli Marzia , Faino Luigi , Ceci Andrea , Maggi Oriana , Persiani Anna Maria , Reverberi Massimo 
Published: March 2022

ABSTRACTThe Antarctic ecosystem is a combination of conditions including extremely low values of temperature. The environmental temperature is one of the parameters thoroughly affecting the structure and composition of fungal membranes lipids. The psychrophilic fungi generally increase the disorder within macromolecules to maintain membrane fluidity at low temperatures. The strategy adopted by Antarctic fungi is to increase the proportion of unsaturated fatty acid that allows maintaining a semi-fluid state of the membranes. This ecological feature might be exploited for using Antarctic fungi as potential alternative source of polyunsaturated fatty acids (PUFAs) for human diet.This study provides both the characterization of fungal strains isolated from Antarctica by lipidomic analysis and the laboratory/large-scale production of fungal biomass with high content of beneficial PUFAs. In detail, three fungal species isolated from environmental matrices from Antarctica were tested and identified at genome level. Growth experiments to evaluate the influence of temperature and substrate in the yield in biomass and unsaturated fatty acid (UFA) were conducted. The results showed that the selected fungi have a high percentage of UFA compared to saturated ones; low growth temperatures increase the yield in linolenic fatty acid (C18:3); the biomass yield depends on the composition of the growth substrate and a satisfying qualitative-quantitative yield has also been obtained by using an agri-food chain waste product as growth substrate.IMPORTANCEThe presence of polyunsaturated fatty acids (PUFAs) in human and animal diet is gaining attention because PUFAs have several recognized functional properties: they modulate immune response, have anti-allergic and anti-inflammatory activity, cardio-protective effect and reduce blood LDL cholesterol levels. Human diets typically do not contain sufficient PUFAs because foods rich in PUFAs are few and it is therefore necessary to supplement this diet. Food supplements with these types of fatty acid currently commercially available come from marine fish oils and this source is no longer sustainable. It is necessary to develop efficient industrial processes capable of producing good quality PUFAs and in quantity, even using as carbon and nitrogen sources agro-industrial chains’ (in our case spent yeast from brewing and whey waste) waste products. Like microorganisms we used Antarctic fungi because they are adapted at very low temperature increasing the proportion of unsaturated fatty acid that allows maintaining a semi-fluid state of the membranes.
SIMMAM 3.0 – Updating the Toolbox for the Conservation of Marine Mammals
Authors: Cabral Alencar , Barreto André S. 
Published: March 2022

AbstractSIMMAM (Sistema de Apoio ao Monitoramento de Mamíferos Marinhos) has been available for marine mammal researchers and environmental agencies in Brazil since 2005. However, it had to be updated, to adapt to new standards and data sharing policies. SIMMAM 3.0 uses more modern technologies (PHP 7.4, Symfony 5.x, PostgreSQL 11.x, PostGIS 3.x, Leaflet 1.7) and is compliant to DarwinCore (DwC) standard and able to exchange data with other data portals that use it. Its database now holds more than 44000 marine mammal records and is an important tool in the decision-making process of Brazilian environmental agencies.
The external validity of four risk scores predicting 30-day mortality after surgery
Authors: Torlot Frederick , Yew Chang-Yang , Reilly Jennifer R. , Phillips Michael , Weber Dieter G. , Corcoran Tomas B. , Ho Kwok M. , Toner Andrew J. 
Published: March 2022

AbstractBackgroundSurgical risk prediction tools can facilitate shared-decision-making and efficient allocation of perioperative resources. Such tools should be externally validated in target populations prior to implementation.MethodsPredicted risk of 30-day mortality was retrospectively derived for surgical patients at Royal Perth Hospital from 2014 to 2021 using the Surgical Outcome Risk Tool (SORT) and the related NZRISK (n=44,031, 53,395 operations). In a sub-population (n=31,153), the Physiology and Operative Severity Score for the enumeration of Mortality (POSSUM) and the Portsmouth variant of this (P-POSSUM) were matched from the Copeland Risk Adjusted Barometer (C2-Ai, Cambridge, UK). The primary outcome was risk score discrimination of 30-day mortality as evaluated by area-under-receiver operator characteristic curve (AUROC) statistics. Calibration plots and outcomes according to risk decile and time were also explored.ResultsAll four risk scores showed high discrimination (AUROC) for 30-day mortality (SORT=0.922, NZRISK=0.909, P-POSSUM=0.893; POSSUM=0.881) but consistently over-predicted risk. SORT exhibited the best discrimination and calibration. Thresholds to denote the highest and second-highest deciles of SORT risk (>3.92% and 1.52-3.92%) captured the majority of deaths (76% and 13% respectively) and hospital-acquired-complications. Year-on-year SORT calibration performance drifted towards over-prediction, reflecting a decrease in 30-day mortality over time despite an increase in the surgical population risk.ConclusionsSORT was the best performing risk score in predicting 30-day mortality after surgery. Categorising patients based on SORT into low, medium (80-90th percentile) and high-risk (90-100th percentile) can guide future allocation of perioperative resources. No tools were sufficiently calibrated to support shared-decision-making based on absolute predictions of risk.
Mapping Multiple Factors Mediated Chromatin Interactions to Assess Regulatory Network and Dysregulation of Lung Cancer-Related Genes
Authors: Zhang Yan , Zhang Jingwen , Zhang Wei , Wang Mohan , Wang Shuangqi , Xu Yao , Zhao Lun , Li Xingwang , Li Guoliang 
Published: March 2022

AbstractStudies on the lung cancer genome are indispensable for developing a cure for lung cancer. Whole-genome resequencing, genome-wide association studies, and transcriptome sequencing have greatly improved our understanding of the cancer genome. However, dysregulation of long-range chromatin interactions in lung cancer remains poorly described. To better understand the three-dimensional (3D) genomic interaction features of the lung cancer genome, we used the A549 cell line as a model system. The generated high-resolution data revealed chromatin interactions associated with RNA polymerase II (RNAPII), CCCTC-binding factor (CTCF), enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), and histone 3 lysine 27 trimethylation (H3K27me3) using specific antibodies and long-read chromatin interaction analysis by paired-end tag sequencing (ChIA-PET). The EZH2/H3K27me3-mediated interactions further silenced target genes, either through loops or domains, and showed distributions along the genome distinct from and complementary to those associated with RNAPII. We found that cancer-related genes were highly enriched in chromatin interactions. We identified abnormal interactions associated with oncogenes and tumor suppressors, such as additional repressive interactions on FOXO4 and promoter – promoter interactions between NF1 and RNF135. Knockout of abnormal interactions reversed the dysregulation of cancer-related genes, suggesting that chromatin interactions are essential for proper expression of lung cancer-related genes. These findings demonstrate the 3D landscape and gene regulatory relationships of the lung cancer genome.
Heterogeneous multimeric metabolite ion species observed in LC-MS based metabolomics data sets
Authors: Abiead Yasin El , Bueschl Christoph , Panzenboeck Lisa , Wang Mingxun , Doppler Maria , Seidl Bernhard , Zanghellini Jürgen , Dorrestein Pieter C. , Koellensperger Gunda 
Published: March 2022

AbstractCovalent or non-covalent heterogeneous multimerization of molecules associated with extracts from biological samples analyzed via LC-MS is quite difficult to recognize/annotate and therefore the prevalence of multimerization remains largely unknown. In this study, we utilized 13C labeled and unlabeled Pichia pastoris extracts to recognize heterogeneous multimers. More specifically, between 0.8% and 1.5% of the biologically-derived features detected in our experiments were confirmed to be heteromers, about half of which we could successfully annotate with monomeric partners. Interestingly, we found specific chemical classes such as nucleotides to disproportionately contribute to heteroadducts. Furthermore, we compiled these compounds into the first MS/MS library that included data from heteromultimers to provide a starting point for other labs to improve the annotation of such ions in other metabolomics data sets. Then, the detected heteromers were also searched in publicly accessible LC-MS datasets available in Metabolights, Metabolomics WB, and GNPS/MassIVE to demonstrate that these newly annotated ions are also relevant to other public datasets. Furthermore, in additional datasets (Triticum aestivum, Fusarium graminearum, and Trichoderma reesei) our developed workflow also detected 0.5% to 4.9% of metabolite features to originate from heterodimers, demonstrating heteroadducts to be present in metabolomics studies at a low percentage.
Remorin proteins serves as membrane topology scaffolds in plants
Authors: Su Chao , Rodriguez-Franco Marta , Lace Beatrice , Nebel Nils , Hernandez-Reyes Casandra , Liang Pengbo , Schulze Eija , Popp Claudia , Keller Jean , Libourel Cyril , Fischer Alexandra A.M. , Gabor Katharina E. , Mymrikov Evgeny V. , Gross Nikolas M. , Mark Eric , Hunte Carola , Weber Wilfried , Wendler Petra , Stanislas Thomas , Delaux Pierre-Marc , Einsle Oliver , Ott Thomas 
Published: March 2022

AbstractOrganization of membrane topologies in plants has so far been mainly attributed to the cell wall and the cytoskeleton. Taking rhizobial infections of legume root cells, where plasma membranes undergo dynamic and large-scale topology changes, as an initial model, we challenged this paradigm and tested whether additional scaffolds such as plant-specific remorins that accumulate on highly curved and often wall-less plasma membrane domains, control local membrane dynamics. Indeed, loss-of-function mutants of the remorin protein SYMREM1 failed to develop stabilized membrane tubes as found in colonized cells in wild-type plants, but released empty membrane spheres instead. Expression of this and other remorins in wall-less protoplasts allowed engineering different membrane topologies ranging from membrane blebs to long membrane tubes. Reciprocally, mechanically induced membrane indentations were equally stabilized by SYMREM1. This function is likely supported by remorin oligomerization into antiparallel dimers and the formation of higher order membrane scaffolding structures. Taken together we describe an evolutionary confined mechanism that allows the stabilization of large-scale membrane conformations and curvatures in plants.One-sentence summaryThe remorin SYMREM1 evolved as structural membrane scaffold that stabilizes membrane tubulation and curvature during symbiotic intracellular infections.
The identification of two newly discovered fluorescent proteins in human glioblastoma
Authors: Lyu Xiao , Wei Yutian 
Published: March 2022

AbstractGlioblastoma (GBM) is a common malignancy featured by an extremely strong proliferation with enriched genetic information. Due to the rapid proliferation and the unstable genome-induced evolutionary potential, unique proteins may be expressed in GBM cells under the certain influence of the microenvironment. We therefore speculated that fluorescent proteins exist in GBM cells. During the immunofluorescence staining assay, we accidently discovered autofluorescence in primary GBM cells without fluorescent labeling, which were further validated as 2 newly discovered fluorescent proteins excited by 467 nm and 378 nm wavelength, respectively, namely human fluorescent protein Ⅰ and Ⅱ (HFP1, HFP2). Fluorescence colocalization and fluorescence resonance energy transfer (FRET) results showed the tight interaction of HFP1 and HFP2, and their synergistic effect. Our results for the first time identified 2 newly discovered fluorescent proteins in GBM cells, and clarified their chemical properties.
Solute exchange through gap junctions lessens the adverse effects of inactivating mutations in metabolite-handling genes
Authors: Monterisi Stefania , Michl Johanna , Hill Amaryllis E. , Hulikova Alzbeta , Abdullayeva Gulnar , Bodmer Walter F. , Swietach Pawel 
Published: March 2022

ABSTRACTExperimental inactivation of certain genes involved in metabolism attenuates cancer cell growth in vitro. However, loss-of-function mutations in metabolic pathways are not negatively selected in human cancers, indicating that these genes are not essential in vivo. We hypothesize that spontaneous mutations affecting metabolic pathways do not necessarily result in a functional defect because affected cells may be rescued by exchanging metabolites with neighboring wild-type cells via gap junctions. Using fluorescent substances to probe inter-cellular diffusion, we show that colorectal cancer (CRC) cells are coupled by gap junctions assembled from connexins, particularly the constitutively expressed Cx26. In co-cultures of wild-type cells with cells that had inactivated components of pH regulation (SLC9A1), glycolysis (ALDOA), or mitochondrial metabolism (NDUFS1), we show that diffusive coupling was able to rescue the functional defect associated with the inactivation of metabolite-handling genes. Function rescue was dependent on Cx26 channels and reduced phenotypic heterogeneity among cells. Since the phenotypic landscape did not map onto genotype, an individual cell should not be considered as the unit under selection, at least in the case of metabolite-handling processes. Our findings can explain why certain loss-of-function mutations in genes, previously ascribed as being ‘essential’, do not influence the growth of human cancers.