Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome

Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity and related diseases, but their mechanistic basis and significance are unclear. Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal excitation. In exploring the basis of these N-glycosylation alterations, we discovered they result from the growth and proliferation of Golgi satellites scattered throughout the dendrite. Golgi satellites that formed with neuronal excitation were in close association with ER exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130. They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway, or on surface glycoproteins taken up from the endocytic pathway. These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors. Neural activity thus boosts the activity of the dendrite’s satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites. This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction and disease.
Millennial-scale change on a Caribbean reef system that experiences hypoxia

Coastal hypoxia has become an increasingly acknowledged threat to coral reefs that is potentially intensifying because of increased input of anthropogenic nutrients. Almirante Bay (Caribbean Panama) is a semi-enclosed system that experiences hypoxia in deeper waters which occasionally expand into shallow coral reefs, suffocating most aerobic benthic life. To explore the long-term history of reefs in the bay we extracted reef matrix cores from two reefs that today experience contrasting patterns of oxygenation. We constructed a 1800-year-long record of gastropod assemblages and isotope compositions from six U-Th chronologically-constrained reef matrix cores. We extracted two cores from each reef at 3 m water depth and two additional cores from a deeper part (4.8 m) of the hypoxia-exposed reef. Results show that the deeper part of the hypoxic reef slowed in growth and stopped accreting approximately 1500 years BP while the shallow part of the reef continued to accrete to the present day, in agreement with a model of expanding hypoxia at this time. Our proxy-based approach suggests that differences among these palaeoindicators in the two reefs may have been driven by an increase in hypoxia via eutrophication caused by either natural changes or human impacts. Similar patterns of increasing herbivores and decreasing carbon isotope values occurred in the shallow part of the hypoxic reef during the last few decades. This suggests that hypoxia may be expanding to depths as shallow as 3 m and that shallow reefs are experiencing greater risk due to increased human activity.
delilah, prospero and D-Pax2 constitute a gene regulatory network essential for the development of functional proprioceptors

Coordinated animal locomotion depends on the development of functional proprioceptors. While early cell-fate determination processes are well characterized, little is known about the terminal differentiation of cells within the proprioceptive lineage and the genetic networks that control them. In this work we describe a gene regulatory network consisting of three transcription factors-Prospero (Pros), D-Pax2 and Delilah (Dei)-that dictates two alternative differentiation programs within the proprioceptive lineage in Drosophila. We show that D-Pax2 and Pros control the differentiation of cap versus scolopale cells in the chordotonal organ lineage by, respectively, activating and repressing the transcription of dei. Normally, D-Pax2 activates the expression of dei in the cap cell but is unable to do so in the scolopale cell where Pros is co-expressed. We further show that D-Pax2 and Pros exert their effects on dei transcription via a 262 bp chordotonal-specific enhancer in which two D-Pax2- and three Pros-binding sites were identified experimentally. When this enhancer was removed from the fly genome, the cap- and ligament-specific expression of dei was lost, resulting in loss of chordotonal organ functionality and defective larval locomotion. Thus, coordinated larval locomotion depends on the activity of a dei enhancer that integrates both activating and repressive inputs for the generation of a functional proprioceptive organ.
Real-time PCR assay for detection and differentiation of Coccidioides immitis and Coccidioides posadasii from culture and clinical specimens

Coccidioidomycosis (Valley Fever) is a pulmonary and systemic fungal disease with increasing incidence and expanding endemic areas. The differentiation of etiologic agents Coccidioides immitis and C. posadasii remains problematic in the clinical laboratories as conventional PCR and satellite typing schemes are not facile. Therefore, we developed Cy5- and FAM-labeled TaqMan-probes for duplex real-time PCR assay for rapid differentiation of C. immitis and C. posadasii from culture and clinical specimens. The RRA2 gene encoding proline-rich antigen 2, specific for Coccidioides genus, was the source for the first set of primers and probe. Coccidioides immitis contig 2.2 (GenBank: AAEC02000002.1) was used to design the second set of primers and probe. The second primers/probe did not amplify the corresponding C. posadasii DNA, because of an 86-bp deletion in the contig. The assay was highly sensitive with limit of detection of 0.1 pg gDNA/PCR reaction, which was equivalent to approximately ten genome copies of C. immitis or C. posadasii. The assay was highly specific with no cross-reactivity to the wide range of fungal and bacterial pathogens. Retrospective analysis of fungal isolates and primary specimens submitted from 1995 to 2020 confirmed 129 isolates and three primary specimens as C. posadasii and 23 isolates as C. immitis from human coccidioidomycosis cases, while all eight primary samples from two animals were confirmed as C. posadasii. A preliminary analysis of cerebrospinal fluid (CSF) and pleural fluid samples showed positive correlation between serology tests and real-time PCR for two of the 15 samples. The Coccidioides spp. duplex real-time PCR will allow rapid differentiation of C. immitis and C. posadasii from clinical specimens and further augment the surveillance of coccidioidomycosis.
Combinatorial interactions between viral proteins expand the functional landscape of the viral proteome

As intracellular parasites, viruses need to manipulate the molecular machinery of their host cells in order to enable their own replication and spread. This manipulation is based on the activity of virus-encoded proteins. The reduced size of viral genomes imposes restrictions in coding capacity; how the action of the limited number of viral proteins results in the massive cell reprogramming observed during the viral infection is a long-standing conundrum in virology. In this work, we explore the hypothesis that combinatorial interactions expand the multifunctionality of viral proteins, which may exert different activities individually and when in combination, physical or functional. We show that the proteins encoded by a plant-infecting DNA virus physically associate with one another in an intricate network. Our results further demonstrate that these interactions can modify the subcellular localization of the viral proteins involved, and that co-expressed interacting viral proteins can exert novel biological functions in planta that go beyond the sum of their individual functions. Based on this, we propose a model in which combinatorial physical and functional interactions between viral proteins enlarge the functional landscape of the viral proteome, which underscores the importance of studying the role of viral proteins in the context of the infection.
OASIS evaluation of the French surveillance network for antimicrobial resistance in diseased animals (RESAPATH): success factors at the basis of a well-performing volunteer system

Antimicrobial resistance is a One Health issue requiring the development of surveillance systems in the human, environmental and animal sectors. In Europe, the surveillance of antimicrobial resistance on zoonotic pathogens and indicator bacteria in healthy food-producing animals has been implemented on a legal basis, while countries are also expected to extend their surveillance to diseased animals in the frame of national action plans. In this context, evaluating existing antimicrobial resistance surveillance systems in veterinary medicine is important to improve systems in place, but also to help other countries learn from these experiences, understand success factors and anticipate challenges. With this aim, the French surveillance network for antimicrobial resistance in bacteria from diseased animals (RESAPATH) was evaluated using the OASIS assessment tool. Key performance factors included (i) a strong and inclusive central institutional organization defining clear and well-accepted surveillance objectives, scope and procedures, (ii) strong skills in epidemiology and microbiology and (iii) a win-win approach enabling the volunteer participation of 71 field laboratories and where a free annual proficiency testing plays a pivotal role. The main area of improvement of RESAPATH was its time-consuming data management system.
Clumpiness: Modeling the Impact of Social Dynamics on COVID-19 Spread

We present an agent based simulation supplemented with two novel social network interconnectivity measures, `clumpiness' and `hoprank,' that are the same concept defined at global and local levels, respectively. The measures may be computed from samples of readily available demographic data, and are useful for measuring probabilistic packet transmission through social networks. For simplicity, agents in our simulation group together through homophily, the principle of `like attracts like'. In three studies we apply clumpiness to measure the effects, on disease transmission, caused by social networks of both homophilic physical proximity and homophilic information replication. The particular characteristic we are interested in about disease transmission is herd immunity, the percentage of a population that has to be immune in order to prevent infection from spreading to those who are not. Two studies demonstrate innovations measuring herd immunity levels and predicting future outbreak locations, procedures relevant to epidemiological control policy. In the first study, we look at how homophilic physical proximity networks form natural bubbles that act as frictive surfaces that affect the speed of transmission of packets and influence herd immunity levels. In the second study, we test clumpiness in homophilic proximity social networks as a predictor of future infection outbreaks at the level of individual schools, restaurants, and workplaces. Our third study demonstrates that protective social bubbles form naturally from homophilic information replication networks, and enhance the natural bubbles that come from the homophilic physical proximity networks. Accurate description of this information environment lays the foundation for epidemiological messaging policy formation.
Simulation of microscale gas flow in heterogeneous porous media based on the lattice Boltzmann method

A microscale multi-relaxation-time lattice Boltzmann model with the regularization procedure is adopted to simulate gas flow in different porous media. The diffuse reflection boundary condition is used to deal with the random solid boundaries. Because of the complex geometry of the pores, the characteristic length is no longer a constant but a function of the pore locations for the porous media. A rational method is proposed to obtain the local characteristic lengths of the porous media for the microscale gas flow simulations. The simulation results show that gas flow characteristics in different flow regions are notably different. In the continuum flow region and slip flow region, the gas flow abilities in different pores are quite different. The effect of heterogeneity of the porous media on gas velocity distribution is very obvious. As the Knudsen number increases, the differences of gas flow abilities in different pores decrease. For gas flow in the strong transition flow region and free molecular flo.
Knockdown of PHYTOENE DESATURASE in the field dodder, Cuscuta campestris, by Virus-Induced Gene Silencing

Cuscuta campestris is a globally distributed obligate holoparasitic plant, and economically important crop pest. There is an urgent need for safe and effective new herbicides to control Cuscuta spp. PHYTOENE DESATURASE (PDS) is a biosynthetic enzyme within the carotenoid synthesis pathway, which is a target for several commercially available herbicides. The low transpiration rate of C. campestris results in sub-optimal translocation of PDS-targeting herbicides throughout the parasite, and resistance to these herbicides, and others, should be anticipated. Here we demonstrate that RNA interference (RNAi) can effectively reduce the expression of PDS in C. campestris. Virus Induced Gene Silencing (VIGS) is capable of inducing PDS knockdown in C. campestris, when Tobacco Rattle Virus (TRV) is used to deliver a PDS-specific sequence through the host plant Arabidopsis thaliana. This leads to a reduction in the accumulation of beta carotene, which is synthesised from phytoene, and significantly reduced growth of C. campestris. We hypothesise that secondary amplification and spread of PDS double-stranded RNA within C. campestris may circumvent the translocation limitations of other xylem and phloem-spread PDS-specific herbicides. These data demonstrate for the first time that VIGS can be used for reverse genetics interrogation of the C. campestris genome.
Selective abrogation of S6K2 maps lipid homeostasis as a survival vulnerability in MAPKi-resistant NRASMUT melanoma

Although oncogenic NRAS activates MAPK signaling, inhibition of the MAPK pathway is not therapeutically efficacious in NRAS-mutant tumors. Here we report that silencing the ribosomal protein S6 kinase 2 (S6K2), while preserving the activity of S6K1, perturbs lipid metabolism, enhances fatty acid unsaturation, triggers lipid peroxidation and induces cell death selectively in NRAS-mutant melanoma cells that are resistant to MAPK inhibition. S6K2 depletion stimulates SREBP1 activity in an S6K1-dependent manner and relieves suppression of PPARα, triggering apoptosis and ferroptosis. Combining PPARα agonists and polyunsaturated fatty acids phenocopies the effects of S6K2 abrogation, blocking tumor growth. Collectively, our study establishes S6K2 and its effector subnetwork as promising targets for NRAS-mutant melanoma that are resistant to global MAPK pathway inhibitors.
A Novel Immune-Related Prognostic Biomarker and Target Associated With Malignant Progression of Glioma

Background Glioma is one of the most common malignancies in the central nervous system and has limited effective therapeutic options. Therefore, we sought to identify a suitable target for immunotherapy. Materials and Methods We screened prognostic genes for glioma in the CGGA database and GSE43378 dataset using survival analysis, receiver operating characteristic (ROC) curves, independent prognostic analysis, and clinical correlation analysis. The results were intersected with immune genes from the ImmPort database through Venn diagrams to obtain likely target genes. The target genes were validated as prognostically relevant immune genes for glioma using survival, ROC curve, independent prognostic, and clinical correlation analyses in samples from the CGGA database and GSE43378 dataset, respectively. We also constructed a nomogram using statistically significant glioma prognostic factors in the CGGA samples and verified their sensitivity and specificity with ROC curves. The functions, pathways, and co-expression-related genes for the glioma target genes were assessed using PPI networks, enrichment analysis, and correlation analysis. The correlation between target gene expression and immune cell infiltration in glioma and the relationship with the survival of glioma patients were investigated using the TIMER database. Finally, target gene expression in normal brain, low-grade glioma, and high-grade glioma tissues was detected using immunohistochemical staining. Results We identified TNFRSF12A as the target gene. Satisfactory results from survival, ROC curve, independent prognosis, and clinical correlation analyses in the CGGA and GSE43378 samples verified that TNFRSF12A was significantly associated with the prognosis of glioma patients. A nomogram was constructed using glioma prognostic correlates, including TNFRSF12A expression, primary-recurrent-secondary (PRS) type, grade, age, chemotherapy, IDH mutation, and 1p19q co-deletion in CGGA samples with an AUC value of 0.860, which illustrated the accuracy of the prognosis prediction. The results of the TIMER analysis validated the significant correlation of TNFRSF12A with immune cell infiltration and glioma survival. The immunohistochemical staining results verified the progressive up-regulation of TNFRSF12A expression in normal brain, low-grade glioma, and high-grade glioma tissues. Conclusion We concluded that TNFRSF12A was a viable prognostic biomarker and a potential immunotherapeutic target for glioma.
Flexible control of Pavlovian-instrumental transfer based on expected reward value

The Pavlovian-instrumental transfer (PIT) paradigm is widely used to assay the motivational influence of reward-predictive cues, reflected by their ability to invigorate instrumental behavior. Leading theories assume that a cue’s motivational properties are tied to predicted reward value. We outline an alternative view which recognizes that reward-predictive cues may suppress rather than motivate instrumental behavior under certain conditions, an effect termed positive conditioned suppression. We posit that cues signaling imminent reward delivery tend to inhibit instrumental behavior, which is exploratory by nature, in order to facilitate efficient retrieval of the expected reward. According to this view, the motivation to engage in instrumental behavior during a cue should be inversely related to the value of the predicted reward, since there is more to lose by failing to secure a high-value reward than a low-value reward. We tested this hypothesis in rats using a PIT protocol known to induce positive conditioned suppression. In Experiment 1, cues signaling different reward magnitudes elicited distinct response patterns. Whereas the 1-pellet cue increased instrumental behavior, cues signaling 3 or 9 pellets suppressed instrumental behavior and elicited high levels of food-port activity. Experiment 2 found that reward-predictive cues suppressed instrumental behavior and increased food-port activity in a flexible manner that was disrupted by post-training reward devaluation. Further analyses suggest that these findings were not driven by overt competition between the instrumental and food-port responses. We discuss how the PIT task may provide a useful tool for studying cognitive control over cue-motivated behavior in rodents.
Testing for pollinator recognition in multiple species of Heliconia

Many plants have evolved floral traits that, in effect, filter pollinator communities and promote pollination by efficient pollinators. Most documented pollinator filter traits act to deter or reduce visitation rates by a subsect of the community of floral visitors. However, a recently described pollinator filter termed ‘pollinator recognition’ (PR) acts at a stage after a pollinator visit. PR was first documented experimentally in Heliconia tortuosa whereby pollen tube germination – a proxy for reproduction – was enhanced following visits from morphologically specialized pollinators, but not generalists. This is thought to promote outcrossing among plants by preferentially investing in reproduction following visits by long-ranging hummingbirds with specialized bill shapes. To date, this plant behavior has only been described in H. tortuosa, but, if widespread, could have important ecological implications; given declines in abundances of specialist pollinators, visits by generalists would not buffer the loss of pollination services to plants with PR. We therefore tested for PR in four taxa spread widely across the Heliconiaceae. We corroborated previous results that visits by long-billed, but not short-billed hummingbirds increased pollen tubes in H. tortuosa with aviary experiments that standardized pollen quality and minimized variation in pollen quantity. Across species, we found great variation in pollen tube responses to experimental treatments. For one species (H. rostrata), we found increased numbers of pollen tubes in those visited by hummingbirds compared to hand pollination alone, regardless of the visiting bird’s bill morphology, indicating recognition of hummingbirds in general. In other cases, hummingbird visits decreased pollen tube counts compared to hand pollinations alone. Furthermore, our results could not substantiate any specific mechanism for pollinator recognition and highlight the need for further work on the complexities of and variability in reproductive strategies across plant taxa.
Listening to the Whispers in Neuroimmune Crosstalk: A Comprehensive Workflow to Investigate Neurotrophin Receptor p75NTR Under Endogenous, Low Abundance Conditions

Inflammatory conditions are critically influenced by neuroimmune crosstalk. Cytokines and neurotrophic factors shape the responses of both nervous and immune systems. Although much progress has been made, most findings to date are based on expression of recombinant (tagged) proteins. The examination of receptor interactions by immunoprecipitation (IP) at endogenous levels provides further insight into the more subtle regulations of immune responses. Here, we present a comprehensive workflow and an optimized IP protocol that provide step-by-step instructions to investigate neurotrophin receptor p75NTR at endogenous, low abundance levels: from lysate preparation and confirmation of receptor expression to antibody validation and successful detection of protein-protein interactions. We employ human melanoma cell line A375 to validate specific antibodies and IP conditions, and apply these methods to explore p75NTR interactions in human leukemic plasmacytoid dendritic cell line PMDC05 detecting 14-3-3ϵ:p75NTR interaction in this cell type. With p75NTR as an exemplary protein, our approach provides a strategy to detect specific interaction partners even under endogenous, low abundance expression conditions.