Miracle-dz/UniFAR-FTUs huggingface dataset:
Marek’s Disease Virus (Gallid alphaherpesvirus 2)-Encoded miR-M2-5p Simultaneously Promotes Cell Proliferation and Suppresses Apoptosis Through RBM24 and MYOD1-Mediated Signaling Pathways

MicroRNAs (miRNAs) have been demonstrated for their involvement in virus biology and pathogenesis, including functioning as key determinants of virally-induced cancers. As an important oncogenic α-herpesvirus affecting poultry health, Marek’s disease virus serotype 1 [Gallid alphaherpesvirus 2 (GaHV-2)] induces rapid-onset T-cell lymphomatous disease commonly referred to as Marek’s disease (MD), an excellent biological model for the study of virally-induced cancer in the natural hosts. Previously, we have demonstrated that GaHV-2-encoded miRNAs (especially those within the Meq-cluster) have the potential to act as critical regulators of multiple processes such as virus replication, latency, pathogenesis, and/or oncogenesis. In addition to miR-M4-5p (miR-155 homolog) and miR-M3-5p, we have recently found that miR-M2-5p possibly participate in inducing MD lymphomagenesis. Here, we report the identification of two tumor suppressors, the RNA-binding protein 24 (RBM24) and myogenic differentiation 1 (MYOD1), being two biological targets for miR-M2-5p. Our experiments revealed that as a critical miRNA, miR-M2-5p promotes cell proliferation via regulating the RBM24-mediated p63 overexpression and MYOD1-mediated IGF2 signaling and suppresses apoptosis by targeting the MYOD1-mediated Caspase-3 signaling pathway. Our data present a new strategy of a single viral miRNA exerting dual role to potentially participate in the virally-induced T-cell lymphomagenesis by simultaneously promoting the cell proliferation and suppressing apoptosis.
Classification of Progression Patterns in Glioblastoma: Analysis of Predictive Factors and Clinical Implications

Background This study was designed to explore the progression patterns of IDH-wildtype glioblastoma (GBM) at first recurrence after chemoradiotherapy. Methods Records from 247 patients who underwent progression after diagnosis of IDH-wildtype GBM was retrospectively reviewed. Progression patterns were classified as either local, distant, subependymal or leptomeningeal dissemination based on the preoperative and serial postoperative radiographic images. The clinical and molecular characteristics of different progression patterns were analyzed. Results A total of 186 (75.3%) patients had local progression, 15 (6.1%) patients had distant progression, 33 (13.3%) patients had subependymal dissemination, and 13 (5.3%) patients had leptomeningeal dissemination. The most favorable survival occurred in patients with local progression, while no significant difference of survival was found among patients with distant progression, subependymal or leptomeningeal dissemination who were thereby reclassified into non-local group. Multivariable analysis showed that chemotherapy was a protective factor for non-local progression, while gender of male, subventricular zone (SVZ) involvement and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation were confirmed as risk factors for non-local progression (P < 0.05). Based on the factors screened by multivariable analysis, a nomogram was constructed which conferred high accuracy in predicting non-local progression. Patients in non-local group could be divided into long- and short-term survivors who differed in the rates of SVZ involvement, MGMT promoter methylation and reirradiation (P < 0.05), and a nomogram integrating these factors showed high accuracy in predicting long-term survivors. Conclusion Patients harboring different progression patterns conferred distinct clinical and molecular characteristics. Our nomograms could provide theoretical references for physicians to make more personalized and precise treatment decisions.
No Tangible Effects of Field-Grown Cisgenic Potatoes on Soil Microbial Communities

DNA modification techniques are increasingly applied to improve the agronomic performance of crops worldwide. Before cultivation and marketing, the environmental risks of such modified varieties must be assessed. This includes an understanding of their effects on soil microorganisms and associated ecosystem services. This study analyzed the impact of a cisgenic modification of the potato variety Desirée to enhance resistance against the late blight-causing fungus Phytophthora infestans (Oomycetes) on the abundance and diversity of rhizosphere inhabiting microbial communities. Two experimental field sites in Ireland and the Netherlands were selected, and for 2 subsequent years, the cisgenic version of Desirée was compared in the presence and absence of fungicides to its non-engineered late blight-sensitive counterpart and a conventionally bred late blight-resistant variety. At the flowering stage, total DNA was extracted from the potato rhizosphere and subjected to PCR for quantifying and sequencing bacterial 16S rRNA genes, fungal internal transcribed spacer (ITS) sequences, and nir genes encoding for bacterial nitrite reductases. Both bacterial and fungal communities responded to field conditions, potato varieties, year of cultivation, and bacteria sporadically also to fungicide treatments. At the Dutch site, without annual replication, fungicides stimulated nirK abundance for all potatoes, but with significance only for cisgenic Desirée. In all other cases, neither the abundance nor the diversity of any microbial marker differed between both Desirée versions. Overall, the study demonstrates environmental variation but also similar patterns of soil microbial diversity in potato rhizospheres and indicates that the cisgenic modification had no tangible impact on soil microbial communities.
Concordance of Risk Tendency Increases User's Satisfaction: Verification of Agents in Cooperative Game Hanabi

The game agents in cooperative game must be not only intelligent but also acceptable to the player to provide a good game experience. A particularly important factor in implementing an acceptable agent is to make the risk-taking tendency closer to the player. People tend to be attracted to people who has same preference and make similar behavior with themselves. Thus, it is estimated that people are also attracted to cooperative game agents who has same tendency. In this study, we implemented two agents with different risk-taking tendencies. Participants evaluated gameplay with each agent. As a result, Participants with a high-risk taking tendency perceived that agents with a high-risk taking tendency understood the rules of the game more. And vice versa. This suggests that it is possible to improve the player's game experience by making the agent's risk tendency similar to the player's one.
Real-Time Parallel Artificial Membrane Permeability Assay Based on Supramolecular Fluorescent Artificial Receptors

Parallel artificial membrane permeability assay (PAMPA) is a screening tool for the evaluation of drug permeability across various biological membrane systems in a microplate format. In PAMPA, a drug candidate is allowed to pass through the lipid layer of a particular well during an incubation period of, typically, 10–16 h. In a second step, the samples of each well are transferred to a UV-Vis–compatible microplate and optically measured (applicable only to analytes with sufficient absorbance) or sampled by mass-spectrometric analysis. The required incubation period, sample transfer, and detection methods jointly limit the scalability of PAMPA to high-throughput screening format. We introduce a modification of the PAMPA method that allows direct fluorescence detection, without sample transfer, in real time (RT-PAMPA). The method employs the use of a fluorescent artificial receptor (FAR), composed of a macrocycle in combination with an encapsulated fluorescent dye, administered in the acceptor chamber of conventional PAMPA microplates. Because the detection principle relies on the molecular recognition of an analyte by the receptor and the associated fluorescence response, concentration changes of any analyte that binds to the receptor can be monitored (molecules with aromatic residues in the present example), regardless of the spectroscopic properties of the analyte itself. Moreover, because the fluorescence of the (upper) acceptor well can be read out directly by fluorescence in a microplate reader, the permeation of the drug through the planar lipid layer can be monitored in real time. Compared with the traditional assay, RT-PAMPA allows not only quantification of the permeability characteristics but also rapid differentiation between fast and slow diffusion events.
Species dispersal mediates opposing influences of a branching network on genetic variation in a metapopulation

In nature, ubiquitous fractal networks can have two but opposing influences, by increasing distal and confluent habitats, respectively, under raising branching complexity on metapopulations9 genetic structure, although this remains poorly understood, particularly regarding the roles of species-specific traits. In this study, we evaluated the integrated influences of network complexity and species dispersal mode/ability on genetic divergence among populations at the catchment scale, using a theoretical framework with empirical genetic data from four sympatric stream macroinvertebrate species. Empirical patterns of spatial genetic structure were attributed to dispersal ability and the species9 habitat specialisation levels. Our theoretical evidence showed that both greater landscape connectivity (via shorter watercourse distance) and greater isolation of distal habitats (e.g. headwater streams) occur in the more-branched networks. These two spatial features have negative and positve influences on genetic divergence, respectively, with their relative importance varying in different species. Watersheds harbouring a higher number of local populations have larger genetic divergence of metapopulations. Downstream- and upstream-biased asymmetric dispersals dictate increases and declines, respectively, in genetic divergence. In addition, distal populations (e.g. in headwaters) have higher genetic independence between themselves under higher levels of downstream-biased asymmetry. A strong association between species features and evolutionary processes (gene flow and genetic drift) mediates the pervasive influences of branching complexity on metapopulation genetic divergence, which highlights the importance of considering species dispersal patterns when developing management strategies in rapid environmental change scenarios.
Reduced CD4+T Cell CXCR3 Expression in Patients With Allergic Rhinitis

While T cells are considered to play a primary role in IgE-mediated atopic diseases, little is known about the systemic variations of T cell subsets from patients with allergic rhinitis (AR). To elucidate the characteristics of peripheral T cells, we analyzed natural killer, B cell, and T cell populations, performed T cell subset construction, and assessed chemokine receptor and associated serum cytokine expression in 25 AR patients and 20 healthy controls. Our results revealed increased levels of CD4+T cells, serum interleukin (IL)-10, IL-6, and interferon (IFN)-γ, and reduced Th1 and Th17 subsets, identified by their chemokine receptors, in AR patients. These results suggest a systemic activation of T cell responses in AR. We further demonstrated that AR patients exhibit significantly reduced CD4+T cell CXCR3 expression, especially in patients with moderate-severe disease severity, demonstrating that CXCR3 is a potential key molecule that hinders the Th1/Th2 balance in AR pathology. Overall, systemic T cell activation occurred in AR patients and CXCR3 dramatically decreased in CD4+T cells, which may ultimately be used as a potential disease and/or therapeutic target.
VAHunt: Warding Off New Repackaged Android Malware in App-Virtualization's Clothing

Repackaging popular benign apps with malicious payload used to be the most common way to spread Android malware. Nevertheless, since 2016, we have observed an alarming new trend to Android ecosystem: a growing number of Android malware samples abuse recent app-virtualization innovation as a new distribution channel. App-virtualization enables a user to run multiple copies of the same app on a single device, and tens of millions of users are enjoying this convenience. However, cybercriminals repackage various malicious APK files as plugins into an app-virtualization platform, which is flexible to launch arbitrary plugins without the hassle of installation. This new style of repackaging gains the ability to bypass anti-malware scanners by hiding the grafted malicious payload in plugins, and it also defies the basic premise embodied by existing repackaged app detection solutions. As app-virtualization-based apps are not necessarily malware, in this paper, we aim to make a verdict on them prior to run time. Our in-depth study results in two key observations: 1) the proxy layer between plugin apps and the Android framework is the core of app-virtualization mechanism, and it reveals the feature of finite state transitions; 2) malware typically loads plugins stealthily and hides malicious behaviors. These insights motivate us to develop a two-layer detection approach, called VAHunt. First, we design a stateful detection model to identify the existence of an app-virtualization engine in APK files. Second, we perform data flow analysis to extract fingerprinting features to differentiate between malicious and benign loading strategies. Since October 2019, we have tested VAHunt in Antiy AVL Mobile Security, a leading mobile security company, to detect more than 139K app-virtualization-based samples. Compared with the ground truth, VAHunt achieves 0.7% false negatives and zero false positive. Our automated detection frees security analysts from the burden of reverse engineering.
At the Intersection of Digital Games, Gender, and Age: A Participant Observational Study with Active Older Women

This paper presents work-in-progress that informs a current understanding of intersectional themes (age, gender, and digital games) that are important, but under-studied, in the player-computer interaction community. This paper draws on a 4-month participant observational study of game play and interest among active older women (aged 63-83, N=14). The results show how gender and age shape digital game interest and play among the participants. For them, being an older woman now means keeping up with the times, being active and helping others. They disregarded digital games that clashed with this identity. When the digital games projected their identity, their play was fun and productive; and led to recommending the games to others. Current and future research activities are outlined.
OpenMTD: A Framework for Efficient Network-Level MTD Evaluation

Moving Target Defense (MTD) represents a way of defending networked systems on different levels. It mainly focuses on shifting the different surfaces of the protected environment. Existing approaches studied on network-level are Port Hopping (PH), which shifts ports, and Network Address Shuffling (NAS), which steadily alters the network addresses of hosts. As a result, the formerly static attack surface now behaves dynamically whilst the relationship of ports to services and network addresses to hosts can be changed. Most MTD approaches have only been evaluated theoretically and comparisons are still lacking. Hence, based on existing results, it is not possible to contrast implementations like PH and NAS in terms of security and network performance. Finally, implementation details are usually not shared publicly. To mitigate these shortcomings, we developed a hybrid platform that evaluates such techniques and reimplemented PH and NAS with additional features such as connection tracker with fingerprinting service and a honeypot module, which is helpful to bypass attackers attempts. We created a common software platform to integrate approaches using the same gateway components and providing graphic network usability. The environment, named OpenMTD, has been open-sourced and works in a modular fashion allowing for easy extensions and future developments. We show that common attacks, starting with a reconnaissance phase were not able to successfully reach vulnerable hosts that are part of the OpenMTD-protected network. A new worm has been developed to spread across the network and the propagation paths showed that OpenMTD can lay the ground for extending protection mechanisms against self-propagating threats.
The Mozart Effect on the Episodic Memory of Healthy Adults Is Null, but Low-Functioning Older Adults May Be an Exception

Literature on the effects of passive music listening on cognitive performance is mixed, showing negative, null or positive results depending on cognitive domain, age group, temporal relation between music and task (background music vs. music before task, the latter known as Mozart effect), or listener-dependent variables such as musical preference. Positive effects of background music on the two components of episodic memory – item and source memory - for verbal materials seem robust and age-independent, and thus deserve further attention. In the current study, we investigated two potential enhancers of music effects on episodic memory: stopping music before task performance (Mozart effect) to eliminate music-related distraction and using preferred music to maximize reward. We ran a main study on a sample of 51 healthy younger adults, along with a pilot study with 12 older adults, divided into low- vs. high functioning according to cognitive performance in a screening test. Against our expectations, Bayesian analyses showed strong evidence that music had no advantage over silence or environmental sounds in younger adults. Preferred music had no advantage either, consistent with the possibility that music-related reward had no impact on episodic memory. Among older adults, low- but not high-functioning participants’ item memory was improved by music – especially by non-preferred music - compared to silence. Our findings suggest that, in healthy adults, prior-to-task music may be less effective than background music in episodic memory enhancement despite decreased distraction, possibly because reward becomes irrelevant when music is stopped before the task begins. Our pilot findings on older adults raise the hypothesis that low-functioning older participants relate to prior-to-task auditory stimulation in deviant ways when it comes to episodic memory enhancement.
Enhancing State-of-the-art Classifiers with API Semantics to Detect Evolved Android Malware

Machine learning (ML) classifiers have been widely deployed to detect Android malware, but at the same time the application of ML classifiers also faces an emerging problem. The performance of such classifiers degrades---or called ages---significantly over time given the malware evolution. Prior works have proposed to use retraining or active learning to reverse and improve aged models. However, the underlying classifier itself is still blind, unaware of malware evolution. Unsurprisingly, such evolution-insensitive retraining or active learning comes at a price, i.e., the labeling of tens of thousands of malware samples and the cost of significant human efforts. In this paper, we propose the first framework, called APIGraph, to enhance state-of-the-art malware classifiers with the similarity information among evolved Android malware in terms of semantically-equivalent or similar API usages, thus naturally slowing down classifier aging. Our evaluation shows that because of the slow-down of classifier aging, APIGraph saves significant amounts of human efforts required by active learning in labeling new malware samples.
Differential expression of BMP antagonists, gremlin and noggin in hydra: antagonism between Wnt and BMP pathways

Mechanisms regulating BMP and Wnt signaling pathways have been widely studied in many organisms. One of the mechanisms by which these pathways are regulated is by binding of extracellular ligands. In the present study, we report studies with two BMP antagonists, gremlin and noggin from Hydra vulgaris Ind-Pune and demonstrate antagonistic relationship between BMP and Wnt pathways. Gremlin was ubiquitously expressed from the body column to head region except in the basal disc and hypostome. During budding, gremlin was expressed predominantly in the budding region suggesting a possible role in budding; this was confirmed in polyps with different stages of buds. Noggin, on the other hand, was predominantly expressed in the endoderm of hypostome, base of the tentacles, lower body column and at the basal disc in whole polyps. During budding, noggin was expressed at the sites of emergence of tentacles suggesting a role in tentacle formation. This was confirmed in alsterpaullone-treated polyps, which showed noggin expression as distinct spots where ectopic organizers and ectopic tentacles eventually formed. Using RT-PCR, we found that up-regulation of Wnt is accompanied with down-regulation of BMP5-8b demonstrating antagonism between the two pathways. Down-regulation of noggin and gremlin, however, occurred only after 24 h recovery. The data suggest that inhibition of BMP pathway by Wnt signaling in hydra does not directly involve noggin and gremlin. Our findings indicate that the BMP/Noggin antagonism evolved early for setting up and/or maintaining the head organizer while involvement of these BMP antagonists during vertebrate axial patterning are recent evolutionary acquisitions. Summary statement We show that setting up of the Organizer by BMP/Noggin antagonism and role of BMP inhibitors in tissue patterning are evolutionarily ancient, probably arising for the first time in hydra
B Cells in Multiple Sclerosis and Virus-Induced Neuroinflammation

Neuroinflammation can be defined as an inflammatory response within the central nervous system (CNS) mediated by a complex crosstalk between CNS-resident and infiltrating immune cells from the periphery. Triggers for neuroinflammation not only include pathogens, trauma and toxic metabolites, but also autoimmune diseases such as neuromyelitis optica spectrum disorders and multiple sclerosis (MS) where the inflammatory response is recognized as a disease-escalating factor. B cells are not considered as the first responders of neuroinflammation, yet they have recently gained focus as a key component involved in the disease pathogenesis of several neuroinflammatory disorders like MS. Traditionally, the prime focus of the role of B cells in any disease, including neuroinflammatory diseases, was their ability to produce antibodies. While that may indeed be an important contribution of B cells in mediating disease pathogenesis, several lines of recent evidence indicate that B cells are multifunctional players during an inflammatory response, including their ability to present antigens and produce an array of cytokines. Moreover, interaction between B cells and other cellular components of the immune system or nervous system can either promote or dampen neuroinflammation depending on the disease. Given that the interest in B cells in neuroinflammation is relatively new, the precise roles that they play in the pathophysiology and progression of different neuroinflammatory disorders have not yet been well-elucidated. Furthermore, the possibility that they might change their function during the course of neuroinflammation adds another level of complexity and the puzzle remains incomplete. Indeed, advancing our knowledge on the role of B cells in neuroinflammation would also allow us to tackle these disorders better. Here, we review the available literature to explore the relationship between autoimmune and infectious neuroinflammation with a focus on the involvement of B cells in MS and viral infections of the CNS.