Miracle-dz/UniFAR-FTUs huggingface dataset:
MiR-873-5p: A Potential Molecular Marker for Cancer Diagnosis and Prognosis

miR-873 is a microRNA located on chromosome 9p21.1. miR-873-5p and miR-873-3p are the two main members of the miR-873 family. Most studies focus on miR-873-5p, and there are a few studies on miR-873-3p. The expression level of miR-873-5p was down-regulated in 14 cancers and up-regulated in 4 cancers. miR-873-5p has many targeted genes, which have unique molecular functions such as catalytic activity, transcription regulation, and binding. miR-873-5p affects cancer development through the PIK3/AKT/mTOR, Wnt/β-Catenin, NF-κβ, and MEK/ERK signaling pathways. In addition, the target genes of miR-873-5p are closely related to the proliferation, apoptosis, migration, invasion, cell cycle, cell stemness, and glycolysis of cancer cells. The target genes of miR-873-5p are also related to the efficacy of several anti-cancer drugs. Currently, in cancer, the expression of miR-873-5p is regulated by a variety of epigenetic factors. This review summarizes the role and mechanism of miR-873-5p in human tumors shows the potential value of miR-873-5p as a molecular marker for cancer diagnosis and prognosis.
Loss of the GARP but not EARP protein complex drives Golgi sterol overload during dendrite remodeling

Membrane trafficking is essential for sculpting neuronal morphology. The GARP and EARP complexes are conserved tethers that regulate vesicle trafficking in the secretory and endolysosomal pathways, respectively. Both complexes contain the Vps51, Vps52, and Vps53 proteins, and a complex-specific protein: Vps54 in GARP and Vps50 in EARP. In Drosophila, we find that both complexes are required for dendrite morphogenesis during developmental remodeling of multidendritic class IV da (c4da) neurons. Having found that sterol accumulates at the trans-Golgi network (TGN) in Vps54KO/KO neurons, we investigated genes that regulate sterols and related lipids at the TGN. Overexpression of oxysterol binding protein (Osbp) or knockdown of the PI4K four wheel drive (fwd) exacerbates the Vps54KO/KO phenotype, whereas eliminating one allele of Osbp rescues it, suggesting that excess sterol accumulation at the TGN is, in part, responsible for inhibiting dendrite regrowth. These findings distinguish the GARP and EARP complexes in neurodevelopment and implicate vesicle trafficking and lipid transfer pathways in dendrite morphogenesis.
The SMOOTH-Robot: A Modular, Interactive Service Robot

The SMOOTH-robot is a mobile robot that—due to its modularity—combines a relatively low price with the possibility to be used for a large variety of tasks in a wide range of domains. In this article, we demonstrate the potential of the SMOOTH-robot through three use cases, two of which were performed in elderly care homes. The robot is designed so that it can either make itself ready or be quickly changed by staff to perform different tasks. We carefully considered important design parameters such as the appearance, intended and unintended interactions with users, and the technical complexity, in order to achieve high acceptability and a sufficient degree of utilization of the robot. Three demonstrated use cases indicate that such a robot could contribute to an improved work environment, having the potential to free resources of care staff which could be allocated to actual care-giving tasks. Moreover, the SMOOTH-robot can be used in many other domains, as we will also exemplify in this article.
Memories of Migrations Past: Sociality and Cognition in Dynamic, Seasonal Environments

Seasonal migrations are a widespread and broadly successful strategy for animals to exploit periodic and localized resources over large spatial scales. It remains an open and largely case-specific question whether long-distance migrations are resilient to environmental disruptions. High levels of mobility suggest an ability to shift ranges that can confer resilience. On the other hand, a conservative, hard-wired commitment to a risky behavior can be costly if conditions change. Mechanisms that contribute to migration include identification and responsiveness to resources, sociality, and cognitive processes such as spatial memory and learning. Our goal was to explore the extent to which these factors interact not only to maintain a migratory behavior but also to provide resilience against environmental changes. We develop a diffusion-advection model of animal movement in which an endogenous migratory behavior is modified by recent experiences via a memory process, and animals have a social swarming-like behavior over a range of spatial scales. We found that this relatively simple framework was able to adapt to a stable, seasonal resource dynamic under a broad range of parameter values. Furthermore, the model was able to acquire an adaptive migration behavior with time. However, the resilience of the process depended on all the parameters under consideration, with many complex trade-offs. For example, the spatial scale of sociality needed to be large enough to capture changes in the resource, but not so large that the acquired collective information was overly diluted. A long-term reference memory was important for hedging against a highly stochastic process, but a higher weighting of more recent memory was needed for adapting to directional changes in resource phenology. Our model provides a general and versatile framework for exploring the interaction of memory, movement, social and resource dynamics, even as environmental conditions globally are undergoing rapid change.
EWS/FLI mediated reprogramming of 3D chromatin promotes an altered transcriptional state in Ewing sarcoma

Ewing sarcoma is a prototypical fusion transcription factor-associated pediatric cancer that expresses EWS/FLI or highly related fusions. EWS/FLI dysregulates transcription to induce and maintain sarcomagenesis, but the mechanisms utilized are not fully understood. We therefore sought to define the global effects of EWS/FLI on chromatin conformation and transcription in Ewing sarcoma. We found that EWS/FLI (and EWS/ERG) genomic localization is largely conserved across multiple patient-derived Ewing sarcoma cell lines. EWS/FLI binding is primarily associated with compartment activation, establishment of topologically-associated domain (TAD) boundaries, enhancer-promoter looping that involve both intra- and inter-TAD interactions, and gene activation. Importantly, local chromatin features provide the basis for transcriptional heterogeneity in regulation of direct EWS/FLI target genes across different Ewing sarcoma cell lines. These data demonstrate a key role of EWS/FLI in mediating genome-wide changes in chromatin configuration and support the notion that fusion transcription factors serve as master regulators through three-dimensional reprogramming of chromatin.
A hymenopteran odorant alerts flies to bury eggs

Ants are ubiquitous and consume insects at all life stages, presumably creating a strong selective pressure for ant avoidance behaviors across insects. The insect egg stage can be especially defenseless against predation given that eggs are usually immobile and unguarded, suggesting insect mothers may have evolved oviposition strategies to minimize the ant predation risk to their offspring. Given the lack of parental care in most insects, these oviposition strategies would likely be innate rather than learned, since insect mothers are not usually present to assess predation of their eggs. Here, we use the vinegar fly Drosophila melanogaster as a model system for examining parental defensive responses to ant presence. Flies usually lay eggs partially inserted into the food substrate, although some are laid on top of the food and a few are inserted deeply into the food. We found that exposure to ants significantly alters fly oviposition depth: the proportion of eggs on the food surface decreased while the proportion of buried eggs increased. Buried eggs survive ant foraging bouts better than surface eggs, showing that this oviposition depth behavior is adaptive. This induced behavior is conserved across the genus Drosophila and is dependent on the fly olfactory system: anosmic mutant flies fail to bury their eggs in the presence of ants, and ant odor extracts are sufficient to induce egg burying. To further delineate the ant lineages to which flies respond, we exposed flies to the odors from numerous species of ants and other insects. Surprisingly, flies buried their eggs in response to the odors of nearly all hymenopterans tested, including hymenopteran groups that flies rarely interact with in nature like bees and paper wasps. Our data suggest that hymenopterans possess a conserved and ancient odorant, and that drosophilids evolved a mechanism for sensing this odorant early in their evolution as a means of protecting their offspring from ant predation. This study sheds light on the ecology and mechanisms underlying a sscommon biotic interaction in nature, that between insect parents ands the ants that would consume their offspring.
Opportunities and Challenges for Machine Learning in Rare Diseases

Rare diseases (RDs) are complicated health conditions that are difficult to be managed at several levels. The scarcity of available data chiefly determines an intricate scenario even for experts and specialized clinicians, which in turn leads to the so called “diagnostic odyssey” for the patient. This situation calls for innovative solutions to support the decision process via quantitative and automated tools. Machine learning brings to the stage a wealth of powerful inference methods; however, matching the health conditions with advanced statistical techniques raises methodological, technological, and even ethical issues. In this contribution, we critically point to the specificities of the dialog of rare diseases with machine learning techniques concentrating on the key steps and challenges that may hamper or create actionable knowledge and value for the patient together with some on-field methodological suggestions and considerations.
Gaussian network model revisited: effects of mutation and ligand binding on protein behavior

The coarse-grained Gaussian network model (GNM), considers only the alpha carbons of the folded protein. Therefore it is not directly applicable to the study of mutation or ligand binding problems where atomic detail is required. This shortcoming is improved by including all atom pairs within the coordination shell of each other into the Kirchoff adjacency matrix. Counting all contacts rather than only alpha carbon contacts diminishes the magnitude of fluctuations in the system. But more importantly, it changes the graph-like connectivity structure, i.e., the Kirchoff adjacency matrix of the protein. This change depends on amino acid type which introduces amino acid specific and position specific information into the classical coarse-grained GNM which was originally modeled in analogy with the phantom network model of rubber elasticity. With this modification, it is now possible to explain the consequences of mutation and ligand binding on residue fluctuations, their pair-correlations and mutual information shared by each pair. We refer to the new model as ‘all-atom GNM’. Using examples from published data we show that the all-atom GNM gives B-factors that are in better agreement with experiment, can explain effects of mutation on long range communication in PDZ domains and can predict effects of GDP and GTP binding on the dimerization of KRAS.
Differences in Carbon Acquisition Could Explain Adaptive Responses in a Baltic Sea Pico-Phytoplankton

Pico-phytoplankton have ample scope to react to environmental change. Nevertheless, we know little about the underlying physiological mechanisms that govern how evolutionary history may affect short-term responses to environmental change. We investigated growth rates and carbon uptake related traits at 15° and 22°C and at different times during the microbial growth curve (lag phase, mid and late exponential) of eight novel strains of Ostreococcus sp. (ca. 1 μm). The strains were isolated from two distinct regions of the Baltic Sea differing in salinity and temperature as well as variability therein from North-East (Bornholm Basin) to South-West (Kiel area). Strains from Kiel area had ca. 10% higher growth rates on average and showed more variation between strains compared to strains from the Bornholm Basin. While biomass increased throughout the experiment in both temperature, CUE (carbon use efficiency, indicative of photosynthetically derived carbon available for growth) was too low to explain positive growth throughout the entire growth curve at 15°C and during the early stages at 22°C. Throughout the growth curve CUE then increased enough to sustain growth, but only at 22°C. Consequently, we then tested whether Ostreococcus use organic carbon to supplement growth when light is not a limiting factor. We show that Ostreococcus qualitatively modulate their potential to grow on organic carbon sources throughout a single growth curve. Based on the differences between CUE and a potential to grow on organic carbon, we postulate a shift in carbon acquisition between inorganic and organic sources in Ostreococcus sp. with potential implications on ecological dynamics within microbial communities.
A Substituted Diphenyl Amide Based Novel Scaffold Inhibits Staphylococcus aureus Virulence in a Galleria mellonella Infection Model

Antimicrobial compounds can combat microbes through modulating host immune defense, inhibiting bacteria survival and growth, or through impeding or inhibiting virulence factors. In the present study, a panel of substituted diphenyl amide compounds previously found to disrupt bacterial quorum sensing were investigated and several were found to promote survival in the Galleria mellonella model when provided therapeutically to treat a Gram-positive bacterial infection from methicillin-resistant Staphylococcus aureus strain MW2. Out of 21 tested compounds, N-4-Methoxyphenyl-3-(4-methoxyphenyl)-propanamide (AMI 82B) was the most potent at disrupting S. aureus virulence and promoted 50% larvae survival at 120 and 96 h when delivered at 0.5 and 5 mg/Kg, respectively, compared to untreated controls (p < 0.0001). AMI 82B did not exhibit G. mellonella toxicity (LC50 > 144 h) at a delivery concentration up to 5 mg/Kg. Further assessment with mammalian cells suggest AMI 82B hemolytic effects against erythrocytes has an HL50 greater than the highest tested concentration of 64 μg/mL. Against HepG2 hepatic cells, AMI 82B demonstrated an LD50 greater than 64 μg/mL. AMI 82B lacked direct bacteria inhibition with a minimal inhibitory concentration that exceeds 64 μg/mL and no significant reduction in S. aureus growth curve at the same concentration. Assessment via qPCR revealed that AMI 82B significantly depressed quorum sensing genes agr, spa, and icaA (p < 0.05). Thus, AMI 82B therapeutic effect against S. aureus in the G. mellonella infection model is likely an influence on bacterial quorum sensing driven virulence factors and provides an interesting hit compound for this medically important pathogen.
Critical Role of Gut Microbiota and Epigenetic Factors in the Pathogenesis of Behçet’s Disease

Behçet’s disease (BD) is a chronic refractory multisystem autoinflammatory disease, characterized by typical clinical features of non-specific vasculitis, oral and genital ulcers, uveitis, as well as skin lesions. The exact etiopathogenesis of BD remains unknown, existing studies have indicated that genetics and environmental factors contribute to the increased development of BD. Recently, several studies have shown that external environmental factors can affect the process of epigenetic modification, and abnormalities of epigenetic factors have been confirmed to be involved in the occurrence of BD. At the same time, abnormalities of gut microbiota (GM) in the body, have also been confirmed to participate in the pathogenesis of BD by regulating the balance of Th17/Tregs. This article reviews the pathogenesis of BD and summarizes numerous clinical studies, focusing on the mechanism of GM and epigenetic factors impacting on BD, and providing new ideas for further elucidating the pathogenesis of BD.
Editorial: Advances in Understanding NeuroHIV Associated Changes in Neuroimmune Communication in the Combined Anti-retroviral Therapy (cART) Era

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, United States, Department of Psychiatry, University of California San Diego, La Jolla, CA, United States, Department of Neuroscience, Lewis Katz School of Medicine, Philadelphia, PA, United States, Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, United States, Department of Molecular and Comparative Pathobiology, School of
Etiology-Specific Remodeling in Ventricular Tissue of Heart Failure Patients and Its Implications for Computational Modeling of Electrical Conduction

With an estimated 64.3 million cases worldwide, heart failure (HF) imposes an enormous burden on healthcare systems. Sudden death from arrhythmia is the major cause of mortality in HF patients. Computational modeling of the failing heart provides insights into mechanisms of arrhythmogenesis, risk stratification of patients, and clinical treatment. However, the lack of a clinically informed approach to model cardiac tissues in HF hinders progress in developing patient-specific strategies. Here, we provide a microscopy-based foundation for modeling conduction in HF tissues. We acquired 2D images of left ventricular tissues from HF patients (n = 16) and donors (n = 5). The composition and heterogeneity of fibrosis were quantified at a sub-micrometer resolution over an area of 1 mm2. From the images, we constructed computational bidomain models of tissue electrophysiology. We computed local upstroke velocities of the membrane voltage and anisotropic conduction velocities (CV). The non-myocyte volume fraction was higher in HF than donors (39.68 ± 14.23 vs. 22.09 ± 2.72%, p < 0.01), and higher in ischemic (IC) than nonischemic (NIC) cardiomyopathy (47.2 ± 16.18 vs. 32.16 ± 6.55%, p < 0.05). The heterogeneity of fibrosis within each subject was highest for IC (27.1 ± 6.03%) and lowest for donors (7.47 ± 1.37%) with NIC (15.69 ± 5.76%) in between. K-means clustering of this heterogeneity discriminated IC and NIC with an accuracy of 81.25%. The heterogeneity in CV increased from donor to NIC to IC tissues. CV decreased with increasing fibrosis for longitudinal (R2 = 0.28, p < 0.05) and transverse conduction (R2 = 0.46, p < 0.01). The tilt angle of the CV vectors increased 2.1° for longitudinal and 0.91° for transverse conduction per 1% increase in fibrosis. Our study suggests that conduction fundamentally differs in the two etiologies due to the characteristics of fibrosis. Our study highlights the importance of the etiology-specific modeling of HF tissues and integration of medical history into electrophysiology models for personalized risk stratification and treatment planning.
Odor motion sensing enables complex plume navigation

Insects can detect bilateral differences in odor concentration between their two antennae, enabling them to sense odor gradients. While gradients aid navigation in simple odor environments like static ribbons, their role in navigating complex plumes remains unknown. Here, we use a virtual reality paradigm to show that Drosophila use bilateral sensing for a distinct computation: detecting the motion of odor signals. Such odor direction sensing is computationally equivalent to motion detection algorithms underlying motion detection in vision. Simulations of natural plumes reveal that odor motion contains valuable directional information absent from the airflow, which Drosophila indeed exploit when navigating natural plumes. Olfactory studies dating back a century have stressed the critical role of wind sensing for insect navigation (Flügge, 1934; Kennedy and Marsh, 1974); we reveal an entirely orthogonal direction cue used by flies in natural environments, and give theoretical arguments suggesting that this cue may be of broad use across the animal kingdom.
A Multiethnic Asian Perspective of Presumed Consent for Organ Donation: A Population-Based Perception Study

Background: Organ shortage is still a world-wide problem, resulting in long waiting lists for kidney, liver, and heart transplant candidates across many transplant centers globally. This has resulted in the move toward presumed consent to increase deceased organ donation rates. However, there remains a paucity of literature on public attitude and barriers regarding the opt-out system, with existing studies limited to Western nations. Therefore, this study aimed to understand public sentiment and different barriers toward organ donation from the perspective of Singapore, a highly diverse and multiethnic Asian society. Methods: A cross-sectional community semi-structured interview was conducted in a public housing estate in Singapore. Pilot test was undertaken before participants were interviewed face-to-face by trained personnel. All statistical evaluations were conducted using Stata. The χ2-test compared subgroups based on patient characteristics while multivariable logistic regression identified predictors of willingness to donate/ assent. Effect estimates were quantified using odds ratio (OR). Findings: Out of 799 individuals, 85% were agreeable to organ donation after death and 81% were willing to assent to donations of family members' organs, which declined by 16% (p < 0.001) after a clinical scenario was presented. Demographic factors including ethnicity, education, marital, and employment status affected willingness to donate and assent. Knowledge correlated significantly with willingness to donate and assent. In particular, knowledge regarding brain death irreversibility had the strongest correlation (AOR 2.15; 95% CI 1.60–2.89). Conclusions: Organ donation rates remain low albeit presumed consent legislation, due to patient-level barriers, including but not limited to knowledge gaps, cultural values, religious backgrounds, and emotional impact at relatives' death. To effectively boost donor rates, it is crucial for policy makers to invest in public education and improve transplant provisions and family protocols.
Reducing Hinge Flexibility of CAR-T Cells Prolongs Survival In Vivo With Low Cytokines Release

Chimeric antigen receptor (CAR)-modified T cells targeting CD19 demonstrate unparalleled responses in B cell malignancies. However, high tumor burden limits clinical efficacy and increases the risk of cytokine release syndrome and neurotoxicity, which is associated with over-activation of the CAR-T cells. The hinge domain plays an important role in the function of CAR-T cells. We hypothesized that deletion of glycine, an amino acid with good flexibility, may reduce the flexibility of the hinge region, thereby mitigating CAR-T cell over-activation. This study involved generating a novel CAR by deletion of two consecutive glycine residues in the CD8 hinge domain of second-generation (2nd) CAR, thereafter named 2nd-GG CAR. The 2nd-GG CAR-T cells showed similar efficacy of CAR expression but lower hinge flexibility, and its protein affinity to CD19 protein was lower than that of 2nd CAR-T cells. Compared to the 2nd CAR-T cells, 2nd-GG CAR-T cells reduced proinflammatory cytokine secretion without diminishing the specific cytotoxicity toward tumor cells in vitro. Furthermore, 2nd-GG CAR-T cells prolonged overall survival in an immunodeficient mouse model bearing NALM-6 when tumor burden was high. This study demonstrated that a lower-flexibility of CD8α hinge improved survival under high tumor burden and reduced proinflammatory cytokines in preclinical studies. While there is potential for improved safety and efficacy, yet this needs validation with clinical trials.