Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of dengue virus 3’UTR RNA binding proteins in mosquitoes reveals that AeStaufen reduces subgenomic flaviviral RNA in saliva

Dengue viruses (DENV) are expanding global pathogens that are transmitted through the bite of mosquitoes, mostly Aedes aegypti. As RNA viruses, DENV rely on RNA-binding proteins (RBPs) to complete their life cycle. Alternatively, RBPs can act as restriction factors that prevent DENV multiplication. While the importance of RBPs is well-supported in humans, there is a dearth of information about their influence on DENV transmission by mosquitoes. Such knowledge could be harnessed to design novel, effective interventions against DENV. Here, we successfully adapted RNA-affinity chromatography coupled with mass spectrometry–a technique initially developed in mammalian cells–to identify RBPs in Ae. aegypti cells. We identified fourteen RBPs interacting with DENV serotype 2 3’UTR, which is involved in the viral multiplication and produces subgenomic flaviviral RNA (sfRNA). We validated the RNA affinity results for two RBPs by confirming that AePur binds the 3’UTR, whereas AeStaufen interacts with both 3’UTR and sfRNA. Using in vivo functional evaluation, we determined that RBPs like AeRan, AeExoRNase, and AeRNase have pro-viral functions, whereas AeGTPase, AeAtu, and AePur have anti-viral functions in mosquitoes. Furthermore, we showed that human and mosquito Pur homologs have a shared affinity to DENV2 RNA, although the anti-viral effect is specific to the mosquito protein. Importantly, we revealed that AeStaufen mediates a reduction of gRNA and sfRNA copies in several mosquito tissues, including the salivary glands and that AeStaufen-mediated sfRNA reduction diminishes the concentration of transmission-enhancing sfRNA in saliva, thereby revealing AeStaufen’s role in DENV transmission. By characterizing the first RBPs that associate with DENV2 3’UTR in mosquitoes, our study unravels new pro- and anti-viral targets for the design of novel therapeutic interventions as well as provides foundation for studying the role of RBPs in virus-vector interactions.
Quantitative Systems Pharmacology Modeling Framework of Autophagy in Tuberculosis: Application to Adjunctive Metformin Host-Directed Therapy

Quantitative systems pharmacology (QSP) modeling of the host immune response against Mycobacterium tuberculosis can inform the rational design of host-directed therapies (HDTs). We aimed to develop a QSP framework to evaluate the effects of metformin-associated autophagy induction in combination with antibiotics. ABSTRACT Quantitative systems pharmacology (QSP) modeling of the host immune response against Mycobacterium tuberculosis can inform the rational design of host-directed therapies (HDTs). We aimed to develop a QSP framework to evaluate the effects of metformin-associated autophagy induction in combination with antibiotics. A QSP framework for autophagy was developed by extending a model for host immune response to include adenosine monophosphate-activated protein kinase (AMPK)-mTOR-autophagy signaling. This model was combined with pharmacokinetic-pharmacodynamic models for metformin and antibiotics against M. tuberculosis. We compared the model predictions to mice infection experiments and derived predictions for the pathogen- and host-associated dynamics in humans treated with metformin in combination with antibiotics. The model adequately captured the observed bacterial load dynamics in mice M. tuberculosis infection models treated with metformin. Simulations for adjunctive metformin therapy in newly diagnosed patients suggested a limited yet dose-dependent effect of metformin on reduction of the intracellular bacterial load when the overall bacterial load is low, late during antibiotic treatment. We present the first QSP framework for HDTs against M. tuberculosis, linking cellular-level autophagy effects to disease progression and adjunctive HDT treatment response. This framework may be extended to guide the design of HDTs against M. tuberculosis.
IFN-induced protein with tetratricopeptide repeats 2 (Ifit2) limits autoimmune inflammation by regulating myeloid cell activation and metabolic activity

Besides anti-viral functions, Type I IFN expresses potent anti-inflammatory properties and is being widely used to treat certain autoimmune conditions, such as multiple sclerosis (MS). In murine model of MS, experimental autoimmune encephalomyelitis (EAE), administration of IFNβ effectively attenuates the disease development. However, the precise mechanisms underlying the treatment remain elusive. In this study, we report that IFN-induced protein with tetratricopeptide repeats 2 (Ifit2), a type I and type III IFN-stimulated gene, plays a previously unrecognized immune regulatory role during autoimmune neuroinflammation. Mice deficient in Ifit2 display greater susceptibility to EAE and escalated immune cell infiltration in the central nervous system. Ifit2 deficiency is also associated with microglial activation and increased myeloid cell infiltration. Unexpectedly, myelin debris clearance and the subsequent remyelination is impaired in Ifit2-/- CNS tissues. Clearing myelin debris is an important property of reparative M2 type myeloid cells to promote remyelination. Indeed, we observed that bone marrow derived macrophages, CNS infiltrating myeloid cells, and microglia from Ifit2-/- mice express cytokine and metabolic genes associated with proinflammatory M1 type subsets. Taken together, our findings uncover a novel regulatory function of Ifit2 in autoimmune inflammation in part by modulating myeloid cell function and metabolic activity.
Sox8 remodels the cranial ectoderm to generate the ear

The vertebrate inner ear arises from a pool of progenitors with the potential to contribute to all the sense organs and cranial ganglia in the head. Here we explore the molecular mechanisms that control ear specification from these precursors. Using a multi-omics approach combined with loss-of-function experiments we identify a core transcriptional circuit that imparts ear identity, along with the first genome-wide characterization of non-coding elements that integrate this information. This analysis places the transcription factor Sox8 at the top of the ear determination network. Introducing Sox8 into cranial ectoderm not only converts non-ear cells into ear progenitors, but also activates the cellular programs for ear morphogenesis and neurogenesis. Thus, Sox8 has the unique ability to remodel transcriptional networks in the cranial ectoderm towards ear identity.
Mobile Robot in Coal Mine Disaster Surveillance

Coal mine disaster is a common occurrence in mines after which rescue operations are immediately needed which is a risky one. The disaster results in increased level of harmful gases like CO and CO2 resulting in decreased O2 level and high temperature. Moreover the explosion might recur, making direct human intervention impossible inside the tunnel for rescue operation. To prevent human and material loss after mine explosion, a Robot is deployed inside the tunnel, which can travel inside the tunnel to sense gas contents, temperature and transmit the signals to the control room. The robot also has a wireless camera which will transmit live video signal to monitor the status inside the tunnel and to control the movement of the robot . The robot is a conveyor belt type robot enabling it to climb up the obstacles and move across debris. The ZigBee technology is used along with RF transceivers to carry out cheap and efficient wireless communication. With the help of this mobile robot, the loss due to coal mine disaster can be reduced and efficient rescue operation can be carried out.
Addressing Compliance in Call Centers with Entity Extraction

Call centers record and store customer-agent conversations for the purpose of coaching, quality assurance and to comply with Industry Regulations . Good amount of these audio recordings contain sensitive information pertaining to their customers’ ﬁnancial or personal details. To ensure data security, compliance and to reduce the risk of abuse/theft, it becomes important to identify such instances in audio recordings and mask these segments. To automate this process, we propose a cascaded system; ﬁrst, Automatic Speech Recognition (ASR) generates transcript and text-to-audio alignment information for an audio recording. Then, Entity Extraction is performed on generated transcripts to identify and locate sensitive information, and the corresponding sensitive segments are masked in audio recordings using alignment information. We introduce a novel system for selective masking of sensitive information in both audio and transcript.
An Update on the Immunotherapy for Oropharyngeal Squamous Cell Carcinoma

Oropharyngeal squamous cell carcinoma (OPSCC) is an uncommon malignancy worldwide. Remarkably, the rising incidence of OPSCC has been observed in many developed countries over the past few decades. On top of tobacco smoking and alcohol consumption, human papillomavirus (HPV) infection has become a major etiologic factor for OPSCC. The radiotherapy-based or surgery-based systemic therapies are recommended equally as first-line treatment, while chemotherapy-based strategy is applied to advanced diseases. Immunotherapy in head and neck squamous cell carcinoma (HNSCC) is currently under the spotlight, especially for patients with advanced diseases. Numerous researches on programmed death-1/programmed death-ligand 1 checkpoint inhibitors have proven beneficial to patients with metastatic HNSCC. In 2016, nivolumab and pembrolizumab were approved as the second-line treatment for advanced metastatic HNSCC by the USA Food and Drug Administration. Soon after, in 2019, the USA Food and Drug Administration approved pembrolizumab as the first-line treatment for patients with unresectable, recurrent, and metastatic HNSCC. It has been reported that HPV-positive HNSCC patients were associated with increased programmed death-ligand 1 expression; however, whether HPV status indicates different treatment outcomes among HNSCC patients treated with immunotherapy has contradicted. Notably, HPV-positive OPSCC exhibits a significantly better clinical response to primary treatment (i.e., radiotherapy, surgery, and chemotherapy) and a more desirable prognosis compared to the HPV-negative OPSCC. This review summarizes the current publications on immunotherapy in HNSCC/OPSCC patients and discusses the impact of HPV infection in immunotherapeutic efficacy, providing an update on the immune landscape and future perspectives in OPSCC.
Internalization of Muscle-Specific Kinase Is Increased by Agrin and Independent of Kinase-Activity, Lrp4 and Dynamin

Muscle-specific kinase (MuSK) is a receptor tyrosine kinase absolutely required for neuromuscular junction formation. MuSK is activated by binding of motor neuron-derived Agrin to low-density lipoprotein receptor related protein 4 (Lrp4), which forms a complex with MuSK. MuSK activation and downstream signaling are critical events during the development of the neuromuscular junction. Receptor tyrosine kinases are commonly internalized upon ligand binding and crosstalk between endocytosis and signaling has been implicated. To extend our knowledge about endocytosis of synaptic proteins and its role during postsynaptic differentiation at the neuromuscular junction, we studied the stability and internalization of Lrp4, MuSK and acetylcholine receptors (AChRs) in response to Agrin. We provide evidence that MuSK but not Lrp4 internalization is increased by Agrin stimulation. MuSK kinase-activity is not sufficient to induce MuSK internalization and the absence of Lrp4 has no effect on MuSK endocytosis. Moreover, MuSK internalization and signaling are unaffected by the inhibition of Dynamin suggesting that MuSK endocytosis uses a non-conventional pathway and is not required for MuSK-dependent downstream signaling.
A Review on Measures to Rejuvenate Immune System: Natural Mode of Protection Against Coronavirus Infection

SARS-CoV-2, a novel Corona virus strain, was first detected in Wuhan, China, in December 2019. As of December 16, 2021, almost 4,822,472 people had died and over 236,132,082 were infected with this lethal viral infection. It is believed that the human immune system is thought to play a critical role in the initial phase of infection when the viruses invade the host cells. Although some effective vaccines have already been on the market, researchers and many bio-pharmaceuticals are still working hard to develop a fully functional vaccine or more effective therapeutic agent against the COVID-19. Other efforts, in addition to functional vaccines, can help strengthen the immune system to defeat the corona virus infection. Herein, we have reviewed some of those proven measures, following which a more efficient immune system can be better prepared to fight viral infection. Among these, dietary supplements like- fresh vegetables and fruits offer a plentiful of vitamins and antioxidants, enabling to build of a healthy immune system. While the pharmacologically active components of medicinal plants directly aid in fighting against viral infection, supplementary supplements combined with a healthy diet will assist to regulate the immune system and will prevent viral infection. In addition, some personal habits, like- regular physical exercise, intermittent fasting, and adequate sleep, had also been proven to aid the immune system in becoming an efficient one. Maintaining each of these will strengthen the immune system, allowing innate immunity to become a more defensive and active antagonistic mechanism against corona-virus infection. However, because dietary treatments take longer to produce beneficial effects in adaptive maturation, personalized nutrition cannot be expected to have an immediate impact on the global outbreak.
What Factors Encourage Young People to Engage in Substance Use? Substance Use and Associated Factors Among Youth in Southwest Ethiopia: A Community-Based Study

Background Substance use indicated the use of psychoactive substances such as alcohol, cigarettes, khat, and illegal drugs. Substance use has varying impacts on the health and socio-economics of countries, and is a major public health concern globally. Currently, substance use is a common public health problem among Ethiopian youth mainly in the city of Jimma. Therefore, this study aimed to assess the magnitude of Cigarette smoking, alcohol drinking, khat chewing, and associated factors among the youth of Jimma town in 2019. Methods A community-based cross-sectional study was conducted among youth of Jimma town from March 2019 to April 2019. A simple random sampling technique was used to select 423 study participants. Data were collected using a structured interviewer-administered questionnaire. The collected data were entered into EPI data manager version 4.4. 1 and transported to SPSS version 23 for data cleaning and analyses. The disruptive study was carried out to determine the prevalence of cigarette smoking, alcohol consumption, and khat chewing. Binary and multivariable analyses were carried out to identify factories associated with cigarette smoking, alcohol consumption, and khat chewing. Finally, adjusted odds ratios (AOR) with 95% confidence intervals (CI) were used to determine the presence and strength of association. Results The current prevalence of cigarette use, alcohol use, and khat use was 16.0, 30.6, and 45.7%, respectively. Factors associated with current smoking use were substance use by siblings, subjective norm factors, and perceived benefits of substance use. Factors associated with current alcohol consumption were youth who highly perceived substance use as important. Factors associated with current khat use were male, substance use by siblings, out-of-school youth, and subjective norms. Concussion The study findings indicated that the prevalence of khat, alcohol, and cigarettes was high among the youth of the city of Jimma. To reduce the prevalence of khat, alcohol, and cigarettes among youth, coordinated efforts from the youth, the government, health professionals, and the community at large are needed.
Reactivation of the Neurogenic Niche in the Adult Zebrafish Statoacoustic Ganglion Following a Mechanical Lesion

Sensorineural hearing loss is caused by the loss of sensory hair cells and/or their innervating neurons within the inner ear and affects millions of people worldwide. In mammals, including humans, the underlying cell types are only produced during fetal stages making loss of these cells and the resulting consequences irreversible. In contrast, zebrafish produce sensory hair cells throughout life and additionally possess the remarkable capacity to regenerate them upon lesion. Recently, we showed that also inner ear neurogenesis continues to take place in the zebrafish statoacoustic ganglion (SAG) well into adulthood. The neurogenic niche displays presumptive stem cells, proliferating Neurod-positive progenitors and a high level of neurogenesis at juvenile stages. It turns dormant at adult stages with only a few proliferating presumptive stem cells, no proliferating Neurod-positive progenitors, and very low levels of newborn neurons. Whether the neurogenic niche can be reactivated and whether SAG neurons can regenerate upon damage is unknown. To study the regenerative capacity of the SAG, we established a lesion paradigm using injections into the otic capsule of the right ear. Upon lesion, the number of apoptotic cells increased, and immune cells infiltrated the SAG of the lesioned side. Importantly, the Neurod-positive progenitor cells re-entered the cell cycle displaying a peak in proliferation at 8 days post lesion before they returned to homeostatic levels at 57 days post lesion. In parallel to reactive proliferation, we observed increased neurogenesis from the Neurod-positive progenitor pool. Reactive neurogenesis started at around 4 days post lesion peaking at 8 days post lesion before the neurogenesis rate decreased again to low homeostatic levels at 57 days post lesion. Additionally, administration of the thymidine analog BrdU and, thereby, labeling proliferating cells and their progeny revealed the generation of new sensory neurons within 19 days post lesion. Taken together, we show that the neurogenic niche of the adult zebrafish SAG can indeed be reactivated to re-enter the cell cycle and to increase neurogenesis upon lesion. Studying the underlying genes and pathways in zebrafish will allow comparative studies with mammalian species and might provide valuable insights into developing cures for auditory and vestibular neuropathies.
Identifying Euglena Gracilis Metabolic and Transcriptomic Adaptations in Response to Mercury Stress

Mercury contamination in aquatic systems poses a serious environmental stress to phototrophic plankton. We used Euglena gracilis to gain an understanding of the physiochemical changes resulting from mercury stress across the transcriptome and metabolome. Using a combination of Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR-MS) and RNA-sequencing, we identified metabolomic and transcriptomic changes both within and outside cellular space after mercury exposure. Metabolic profiles of E. gracilis were less diverse after mercury exposure, highlighting an overall refinement of metabolites produced. Significant fold changes in cysteine, glutathione, and amino acid-based metabolites were significantly higher (p < 0.05) within the mercury exposed cells and in extracellular space than in untreated cultures. Using integrated omics analyses, a significant upregulation of transcripts and metabolites involved in amino acid synthesis, cellular responses to chemical stress, reactive oxygen species detoxification, and electron transport were identified. Together the enrichment of these pathways highlights mechanisms that E. gracilis harness to mitigate oxidative stress at sublethal concentrations of mercury exposure and give rise to new biomarkers of environmental stress in the widely distributed E. gracilis.
Spatial and Temporal Patterns of Symbiont Colonization and Loss During Bleaching in the Model Sea Anemone Aiptasia

The ability of symbionts to recolonize their hosts after a period of dysbiosis is essential to maintain a resilient partnership. Many cnidarians rely on photosynthate provided from a large algal symbiont population. Under periods of thermal stress, symbiont densities in host cnidarians decline, and the recovery of hosts is dependent on the re-establishment of symbiosis. The cellular mechanisms that govern this process of colonization are not well-defined and require further exploration. To study this process in the symbiotic sea anemone model Exaiptasia diaphana, commonly called Aiptasia, we developed a non-invasive, efficient method of imaging that uses autofluorescence to measure the abundance of symbiont cells, which were spatially distributed into distinct cell clusters within the gastrodermis of host tentacles. We estimated cell cluster sizes to measure the occurrence of singlets, doublets, and so on up to much larger cell clusters, and characterized colonization patterns by native and non-native symbionts. Native symbiont Breviolum minutum rapidly recolonized hosts and rapidly exited under elevated temperature, with increased bleaching susceptibility for larger symbiont clusters. In contrast, populations of non-native symbionts Symbiodinium microadriaticum and Durusdinium trenchii persisted at low levels under elevated temperature. To identify mechanisms driving colonization patterns, we simulated symbiont population changes through time and determined that migration was necessary to create observed patterns (i.e., egression of symbionts from larger clusters to establish new clusters). Our results support a mechanism where symbionts repopulate hosts in a predictable cluster pattern, and provide novel evidence that colonization requires both localized proliferation and continuous migration.
DeepClaw 2.0: A Data Collection Platform for Learning Human Manipulation

Besides direct interaction, human hands are also skilled at using tools to manipulate objects for typical life and work tasks. This paper proposes DeepClaw 2.0 as a low-cost, open-sourced data collection platform for learning human manipulation. We use an RGB-D camera to visually track the motion and deformation of a pair of soft finger networks on a modified kitchen tong operated by human teachers. These fingers can be easily integrated with robotic grippers to bridge the structural mismatch between humans and robots during learning. The deformation of soft finger networks, which reveals tactile information in contact-rich manipulation, is captured passively. We collected a comprehensive sample dataset involving five human demonstrators in ten manipulation tasks with five trials per task. As a low-cost, open-sourced platform, we also developed an intuitive interface that converts the raw sensor data into state-action data for imitation learning problems. For learning-by-demonstration problems, we further demonstrated our dataset’s potential by using real robotic hardware to collect joint actuation data or using a simulated environment when limited access to the hardware.