Miracle-dz/UniFAR-FTUs huggingface dataset:
New perspectives on the calculation of bioaccumulation metrics for active substances in living organisms

Today, only few ready-to-use and convenient decision-making tools are available in ecotoxicology concerning accumulation and effects of chemical substances on organisms, accounting for exposure situations that are known to be complex (routes of exposure, metabolism, mixtures, etc.). This paper presents new perspectives on the generic calculation of bioaccumulation metrics via the innovative web tool MOSAICbioacc (http://mosaic.univ-lyon1.fr/bioacc). MOSAICbioacc provides all kind of bioaccumulation metrics associated with their uncertainty whatever the species-compound combination. MOSAICbioacc expects accumulation-depuration data as inputs, even with complex exposure and clearance patterns, to quickly perform their relevant analysis. MOSAICbioacc intends to facilitate the daily work of regulators, or any ecotoxicologist, who will freely benefit from a user-friendly on-line interface that automatically fits toxicokinetic models without needs for users to invest in the technical aspects to get bioaccumulation metrics estimates. MOSAICbioacc also provides all results in a fully transparent way to ensure reproducibility.
Dissecting Nck/Dock Signaling Pathways in Drosophila Visual System

ac ct t The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility. Ke ey y wor rds s axon guidance, neuronal target recognition, signal transduction, fly visual system.
Urban living influences the reproductive success of Darwin’s finches in the Galápagos Islands

Urbanization is expanding worldwide and can have major consequences for organisms, anthropogenic factors can reduce the fitness of animals but may also have benefits, such as consistent human food availability. Understanding these trade-offs is critically important in environments with unreliable annual natural food availability, such as the Galápagos Islands where urbanization is rapidly increasing. For example, during dry climatic condition years, the reproductive success of bird species, such as Darwin’s finches, is low because low precipitation reduces food availability. Urban areas in the Galápagos provide supplemental human food to finches, which could improve their reproductive success during years with low natural food availability. However, urban finches might face trade-offs, as the incorporation of anthropogenic debris (e.g. string, hair, plastic) into their nests can increase mortality. In our study, we determined the effect of urbanization on the reproductive effort and success of small ground finches (Geospiza fuliginosa; a species of Darwin’s finch) during a dry year on San Cristóbal Island, Galápagos Islands. We also documented the abundance of anthropogenic debris incorporated in to nests. We quantified nest building, egg laying, hatching, and fledging of small ground finches in an urban and non-urban area. We also qualified the type of anthropogenic debris in finch nests and the quantified the percent of debris comprising total nest mass. We determined whether incorporating these materials into the nest directly led to entanglement- or ingestion-related mortalities. Overall, urban finches built more nests, laid more eggs, and produced more fledglings than non-urban finches. However, every nest in the urban area contained anthropogenic-related material, which resulted in entanglement- or ingestion-related mortalities in 18% of nests with nestlings. Non-urban nests did not contain any anthropogenic-related material. Our study showed that urban living has trade-offs during drier climatic conditions: urban birds have overall higher reproductive success than non-urban birds, but urban birds can also suffer a negative consequence by using anthropogenic-related material for nesting. These results suggest that despite the potential cost of urban living, finches benefit overall from urban living and urbanization may buffer the effects of limited resource availability in the Galápagos Islands.
Effect of urea spray on the crop regulation of guava cv. Allahabad safeda

In order to get maximum winter and minimum rainy season crop of guava, cv. Allahabad Safeda, the trees were sprayed with aqueous solutions of urea of different concentration. The first spray was done during the last week of April/first week of May followed by second spray at an interval of 15 days. With the increase in the concentration of urea, rate of defoliation/deblossoming increased. 15 per cent urea spray was found to be optimum in regulating the guava crop with no adverse effect on the yield and quality of fruit.
La estimulación de TLR, receptores tipo NOD y dectina-1 en neutrófilos humanos induce la producción de citocinas proinflamatorias

Objetivo. Evaluar la expresión/función de receptores de reconocimiento de patrones (PRR) como los receptores tipo Toll, receptores tipo NOD, RIG-I/MDA5, Dectina-1 y moléculas adaptadoras, en neutrófilos humanos. Procedimientos básicos. A partir de sangre periférica de individuos sanos se purificó y cultivó neutrófilos en medio RMPI-1640, en presencia o ausencia de lipopolisacárido. Para los ensayos de funcionalidad, los neutrófilos fueron estimulados con agonistas específicos de los receptores de interés. La expresión de los receptores de reconocimiento de patrones se determinó por RT-PCR y la secreción de citoquinas proinflamatorias por ELISA. Hallazgos. Los neutrófilos expresan un amplio espectro de PRR y de moléculas adaptadoras. La estimulación de TLR4, TLR5, TLR7/8 induce la secreción de IL-1β e IL-6; la activación de Dectina-1 induce una alta producción de TNF-α, pero bajos niveles de IL-1β e IL-6. Conclusión. Los neutrófilos expresan un amplio número de PRR y su activación conlleva a la expresión de diferentes citoquinas proinflamatorias. Palabras clave: receptores de reconocimiento de patrones; neutrófilos; Receptores Toll-Like ; Proteínas adaptadoras de señalización NOD; citoquinas; inflamación.
Comparative study on dissolved N and P loss and eutrophication risk in runoff water in contour and down-slope

In contour tillage system, the direction of the plant lines was against the slope, resulting in a decrease of runoff and sediment loss with respect to traditional down-slope tillage. The objective of this work was to analyze the differences of NO 3 -N, NH 4 + -N and P loss in runoff water with the intention of observing possible eutrophication risks in this water, in contour and down-slope. The work was carried out on brown soil with conventional cultivation of peanut. Simulating rainfall of two different intensities (40 mm·h -1 and 70 mm·h -1 ) was used in the study at the beginning of September, 2008. The results showed, under the same rainfall intensity, the concentration of P in runoff water was higher in contour than in downslope tillage, while the concentration differences of NO 3 -N and NH 4 + -N between the two tillage methods were not consistent. Contour can effectively reduce the runoff and the losses of dissolved inorganic nitrogen (NO 3 -N + NH 4 + -N) and P in runoff water compared to down-slope tillage, which will be more obvious under the conditions of high rainfall intensity. The losses of dissolved inorganic nitrogen and P in runoff water were 43% and 5% less, respectively, in contour than in down-slopes tillage at the 40 mm·h -1 rainfall intensity, and were 68% and 55%, respectively, at 70 mm·h -1 . The N/P ratios in runoff water produced by contour and down-slope tillage suggest a certain eutrophication risk in water, which shows an increasing trend within the rainfall process. Compared with down-slope tillage, contour cannot only hinder the increasing trend of eutrophication risk, but also can significantly lower the risk level, and thus effectively reduce the effect of agricultural runoff on eutrophication.
A Transgenic Line That Reports CSF1R Protein Expression Provides a Definitive Marker for the Mouse Mononuclear Phagocyte System

Key Points We have inserted a FRed reporter cassette into the mouse Csf1r locus. Expression of CSF1R-FRed is restricted to cells of the mononuclear phagocyte lineage. CSF1R-FRed is absent from lineage-negative stem cell populations in bone marrow. The proliferation, differentiation, and survival of cells of the mononuclear phagocyte system (MPS; progenitors, monocytes, macrophages, and classical dendritic cells) are controlled by signals from the M-CSF receptor (CSF1R). Cells of the MPS lineage have been identified using numerous surface markers and transgenic reporters, but none is both universal and lineage restricted. In this article, we report the development and characterization of a CSF1R reporter mouse. A FusionRed (FRed) cassette was inserted in-frame with the C terminus of CSF1R, separated by a T2A-cleavable linker. The insertion had no effect of CSF1R expression or function. CSF1R-FRed was expressed in monocytes and macrophages and absent from granulocytes and lymphocytes. In bone marrow, CSF1R-FRed was absent in lineage-negative hematopoietic stem cells, arguing against a direct role for CSF1R in myeloid lineage commitment. It was highly expressed in marrow monocytes and common myeloid progenitors but significantly lower in granulocyte-macrophage progenitors. In sections of bone marrow, CSF1R-FRed was also detected in osteoclasts, CD169+ resident macrophages, and, consistent with previous mRNA analysis, in megakaryocytes. In lymphoid tissues, CSF1R-FRed highlighted diverse MPS populations, including classical dendritic cells. Whole mount imaging of nonlymphoid tissues in mice with combined CSF1R-FRed/Csf1r-EGFP confirmed the restriction of CSF1R expression to MPS cells. The two markers highlight the remarkable abundance and regular distribution of tissue MPS cells, including novel macrophage populations within tendon and skeletal muscle and underlying the mesothelial/serosal/capsular surfaces of every major organ. The CSF1R-FRed mouse provides a novel reporter with exquisite specificity for cells of the MPS.
Chronic High Glyphosate Exposure Delays Individual Worker Bee (Apis mellifera L.) Development under Field Conditions

The ongoing debate about glyphosate-based herbicides (GBH) and their implications for beneficial arthropods give rise to controversy. This research was carried out to cover possible sublethal GBH effects on brood and colony development, adult survival, and overwintering success of honey bees (Apis mellifera L.) under field conditions. Residues in bee relevant matrices such as nectar, pollen and plants were measured in addition. To address these questions, we adopted four independent study approaches. For brood effects and survival, we orally exposed mini-hives housed in the “Kieler mating-nuc” system to sublethal concentrations of 4.8 mg glyphosate/kg (T1, low) and 137.6 mg glyphosate/kg (T2, high) over the period of one brood cycle (21 days). Brood development and colony conditions were assessed after a modified OECD method (No. 75). For adult survival, we weighed and labeled freshly emerged workers from exposed colonies and introduced them into non-contaminated mini-hives to monitor life span for 25 consecutive days. Results from these experiments showed a trivial effect of GBH on colony conditions and survival of individual workers, even though hatching weight was reduced in T2. The brood termination rate (BTR) in the T2 treatment, however, was more than doubled (49.84%) when compared to the control (22.11%) or T1 (20.69%). This was surprising as T2 colonies gained similar weight and similar numbers of bees per colony compared to the control, indicating equal performance. Obviously, the brood development in T2 was not “terminated” as expected by the OECD method terminology but rather “slowed down” for an unknown period of time. In light of these findings, we suggest that chronic high GBH exposure is capable of delaying worker brood development to a significant extent while no further detrimental effects seem to appear at the colony level. Against this background, we discuss additional results and possible consequences of GBH for honey bee health.
TranSynergy: Mechanism-driven interpretable deep neural network for the synergistic prediction and pathway deconvolution of drug combinations

Motivation Drug combinations have demonstrated great potential in cancer treatments. They alleviate drug resistance and improve therapeutic efficacy. With the fast-growing number of anti-cancer drugs, the experimental investigation of all drug combinations is costly and time-consuming. Computational techniques can improve the efficiency of drug combination screening. Despite recent advances in applying machine learning to synergistic drug combinations prediction, several challenges remain. First, the performance of existing methods is suboptimal. There is still much space for improvement. Second, biological knowledge has not been fully incorporated into the model. Finally, many models are lack of interpretability, limiting their clinical applications. Results We develop a knowledge-enabled and self-attention boosted deep learning model, TranSynergy, to improve the performance and interpretability of synergistic drug combinations prediction. TranSynergy is well designed such that cellular effect of drug actions can be explicitly modeled through cell-line gene dependency, gene-gene interaction, and genome-wide drug-target interaction. A novel Shapley Additive Gene Set Enrichment Analysis (SA-GSEA) method is developed to deconvolute biological pathways that contribute to the synergistic drug combination and improve model interpretability. Extensive benchmark studies demonstrate that TranSynergy significantly outperforms the state-of-the-art method, suggesting the potential of mechanism-driven machine learning. Novel pathways that are associated with the synergistic combinations are revealed and supported by experimental evidence. They may provide new insights into identifying biomarkers for precision medicine and discovering new anti-cancer therapies. Several new synergistic drug combinations are predicted with high confidence for ovarian cancer which has few treatment options. Availability The code is available at https://github.com/qiaoliuhub/drug_combination Contact lxie@iscb.org
Structure based Functional Distinction between Cln1 and Cln2 Depends onthe Ubiquitin-Proteasome Pathway

Cln1 and Cln2, G1/S cyclins of the ascomycetous budding yeast Saccharomyces cerevisiae (S. cerevisiae), oscillate during the cell cycle, rising in late G1 and falling in early S phase. We have been tried to elucidate the structure basis of the functional distinction between Cln1 and Cln2. Here we performed in silico simulations: construction and evaluation of three dimensional structures of Cln1-Cdc28 and Cln2-Cdc28 complexes. Our in silico simulations suggested that the interaction of Cln1 and Cln2 with Cdc28 were in the two distinct situations, designated as flip and flop conformation, at the extra amino acid region in the cyclin box of Cln1 and Cln2. We speculated the trigger of this flip-flop conversion of the extra amino acid region in the cyclin box of Cln1-Cdc28 and Cln2-Cdc28 might be regulated by the ubiquitination of the sequences rich in Pro (P), Glu (E), Ser (S) and Thr (T), so-called PEST motifs, in Cln1 and Cln2. Furthermore, we presumed that the functional superiority between Cln1 and Cln2 in the G1/S phase of S. cerevisiae might be controlled by flip-flop conversion and ubiquitin-proteasome pathway.
Horseshoe Bats Recognise the Sex of Conspecifics from Their Echolocation Calls

Echolocation calls produced by bats contain information on the emitter that could be used in social interactions. Nevertheless, little is known about the whether such information actually is being used by bats. Here we tested the ability of two horseshoe bat species (Rhinolophus mehelyi and R. euryale; n = 20 each) to discriminate conspecific male from conspecific female echolocation calls and vice versa. Behavioural data from a habituation-discrimination paradigm revealed that both species were able to recognize the sex of conspecifics from their calls, providing evidence that cues on the sex of the emitter are encoded in echolocation signals. While our data support that the sex-specific acoustic cues are not (just) the horseshoe bats' constant-frequency call part, their nature remains enigmatic. This is the second study to show that bats can recognize the caller's gender from echolocation calls and the first to do so for ‘high-duty-cycle bats’; those that use calls with a prominent constant-frequency (CF) component.
Antagonistic co-contraction can minimize muscular effort in systems with uncertainty

Muscular co-contraction of antagonistic muscle pairs is often observed in human movement, but it is considered inefficient and it can currently not be predicted in simulations where muscular effort or metabolic energy is minimized. Here, we investigated the relationship between minimizing effort and muscular co-contraction in systems with random uncertainty to see if muscular co-contraction can minimize effort in such system. We also investigated the effect of time delay in the muscle, by varying the time delay in the neural control as well as the activation time constant. We solved optimal control problems for a one-degree-of-freedom pendulum actuated by two identical antagonistic muscles, using forward shooting, to find controller parameters that minimized muscular effort while the pendulum remained upright in the presence of noise added to the moment at the base of the pendulum. We compared a controller with and without feedforward control. Task precision was defined by bounding the root mean square deviation from the upright position, while different perturbation levels defined task difficulty. We found that effort was minimized when the feedforward control was nonzero, even when feedforward control was not necessary to perform the task, which indicates that co-contraction can minimize effort in systems with uncertainty. We also found that the optimal level of co-contraction increased with time delay, both when the activation time constant was increased and when neural time delay was added. Furthermore, we found that for controllers with a neural time delay, a different trajectory was optimal for a controller with feedforward control than for one without, which indicates that simulation trajectories are dependent on the controller architecture. Future movement predictions should therefore account for uncertainty in dynamics and control, and carefully choose the controller architecture. The ability of models to predict co-contraction from effort or energy minimization has important clinical and sports applications. If co-contraction is undesirable, one should aim to remove the cause of co-contraction rather than the co-contraction itself.
WormPose: Image synthesis and convolutional networks for pose estimation in C. elegans

An important model system for understanding genes, neurons and behavior, the nematode worm C. elegans naturally moves through a variety of complex postures, for which estimation from video data is challenging. We introduce an open-source Python package, WormPose, for 2D pose estimation in C. elegans, including self-occluded, coiled shapes. We leverage advances in machine vision afforded from convolutional neural networks and introduce a synthetic yet realistic generative model for images of worm posture, thus avoiding the need for human-labeled training. WormPose is effective and adaptable for imaging conditions across worm tracking efforts. We quantify pose estimation using synthetic data as well as N2 and mutant worms in on-food conditions. We further demonstrate WormPose by analyzing long (∼ 10 hour), fast-sampled (∼ 30 Hz) recordings of on-food N2 worms to provide a posture-scale analysis of roaming/dwelling behaviors.
Acetylcholine synergizes with netrin-1 to drive persistent firing in the entorhinal cortex

The ability of the mammalian brain to maintain spatial representations of external or internal information for short periods of time has been associated with sustained neuronal spiking and reverberatory neural network activity in the medial entorhinal cortex. Here, we show that cholinergic activation of muscarinic receptors on entorhinal cortical neurons mediates plasma membrane recruitment of the netrin-1 receptor deleted-in-colorectal cancer (DCC) to promote muscarinic receptor-mediated persistent firing. Conditional deletion of netrin-1 or DCC, which are required for synaptic plasticity, inhibits cholinergic persistent firing, and leads to deficits in spatial working memory. Together, these findings indicate that normal working memory function requires synergistic action of acetylcholine and netrin-1.
Combined Effect of Shear Stress and Laser-Patterned Topography on Schwann cell Outgrowth: Synergistic or Antagonistic?

Although the peripheral nervous system exhibits a higher rate of regeneration than that of the central nervous system through a spontaneous regeneration after injury, the functional recovery is fairly infrequent and misdirected. Thus, the development of successful methods to guide neuronal outgrowth, in vitro, is of great importance. In this study, a precise flow controlled microfluidic system with specific custom-designed chambers, incorporating laser-microstructured polyethylene terephthalate (PET) substrates comprising microgrooves, was fabricated to assess the combined effect of shear stress and topography on Schwann cells’ behavior. The microgrooves were positioned either parallel or perpendicular to the direction of the flow inside the chambers. Additionally, the cell culture results were combined with computational flow simulations to calculate accurately the shear stress values. Our results demonstrated that wall shear stress gradients may be acting either synergistic or antagonistic depending on the substrates groove orientation relative to the flow direction. The ability to control cell alignment in vitro could potentially be used in the fields of neural tissue engineering and regenerative medicine.
Genetic manipulation of the optical refractive index in living cells

The optical refractive index of cellular components is generally not a property considered amenable to manipulation in microscopy as this is an intrinsic physical property of materials. Here we show that by targeting cephalopod reflectin protein nanoparticles one can manipulate the optical refractive index of mammalian cellular compartments. We further demonstrate that refractive index alteration based contrast agents can be utilized for dark field microscopy and quantitative phase contrast holotomography. Additionally we have molecularly cloned novel reflectins with improved and novel optical properties.