Miracle-dz/UniFAR-FTUs huggingface dataset:
A 5′ UTR GGN repeat controls localisation and translation of a potassium leak channel mRNA through G-quadruplex formation

Abstract RNA G-quadruplexes (G4s) are secondary structures proposed to function as regulators of post-transcriptional mRNA localisation and translation. G4s within some neuronal mRNAs are known to control distal localisation and local translation, contributing to distinct local proteomes that facilitate the synaptic remodelling attributed to normal cellular function. In this study, we characterise the G4 formation of a (GGN)13 repeat found within the 5′ UTR of the potassium 2-pore domain leak channel Task3 mRNA. Biophysical analyses show that this (GGN)13 repeat forms a parallel G4 in vitro exhibiting the stereotypical potassium specificity of G4s, remaining thermostable under physiological ionic conditions. Through mouse brain tissue G4-RNA immunoprecipitation, we further confirm that Task3 mRNA forms a G4 structure in vivo. The G4 is inhibitory to translation of Task3 in vitro and is overcome through activity of a G4-specific helicase DHX36, increasing K+ leak currents and membrane hyperpolarisation in HEK293 cells. Further, we observe that this G4 is fundamental to ensuring delivery of Task3 mRNA to distal primary cortical neurites. It has been shown that aberrant Task3 expression correlates with neuronal dysfunction, we therefore posit that this G4 is important in regulated local expression of Task3 leak channels that maintain K+ leak within neurons.
Defining the Concomitant Multiple Organ Injury within the ARS and DEARE in an Animal Model Research Platform.

UNDERSTANDING THE context of the radiation exposure scenario was essential to defining the requirements for relevant animal models that mimicked the human response to acute, high-dose, potentially lethal radiation exposure and its treatment. Our rationale for establishing the animal model research platform was based on several requirements. These were (a) to evaluate and understand the key organ-specific and multi-organ sequelae that are survivable in a realistic nuclear radiation scenario, such as gastrointestinal (GI), hematopoietic (H), acute radiation syndrome (ARS), acute kidney injury (AKI), prolonged GI damage, prolonged immunosuppression, significant loss of body weight, and delayed multi-organ injury (MOI) to include the lung, kidney, and heart injury; (b) to define the radiation dose, incidence, severity, and time-dependent relationships for acute and delayed sequelae; (c) to determine the onset, incidence, severity, progression, and resolution or durability of organ injury and associated doseand time-dependent co-morbidities to include their subject-based medical management; (d) to determinehow tomodel the key sequelae in a “linked” fashion; theARS and delayed effects of acute radiation exposure (DEARE) are composites of doseand multi-organ-damage that may occur in an attendant and/or a sequential manner; (e) to develop a model(s) that will permit definition of the attendant and concurrent organ-specific damage that is essential to development of a “polypharmacy” medical countermeasure (MCM) approach to determine the most effective treatment paradigm for MOI; and (f) to establish a multidisciplinary approach to identify and characterize biomarkers that will predict clinical outcome. Organ-specific MCM may have significant effects on the latency, incidence, severity, and progression of “other” organ damage, as well as assessing the efficacy of MCM combinations for two or more sequelae. The models of partial body irradiation (PBI) with approximately 2.5 or 5% bone marrow (BM) sparing (PBI/BM) in the NHP, rat, and mouse; and the mouse model that focused on the survivors of total body irradiation (TBI)-induced H-ARS will provide invaluable insight into the interaction and potential causal relationships between the ARS and DEARE (Johnston et al. 2011; Booth et al. 2015; MacVittie et al. 2015a, 2019; Unthank et al. 2015; Fish et al. 2016; Cohen et al. 2017, 2019; Chua et al. 2019; Farese et al. 2019; Jacobs et al. 2019; Medhora et al. 2019; Parker et al. 2019a–c; Unthank et al. 2019; Fish et al. 2020). TBI and whole thorax lung irradiation (WTLI) models are organ-focused (GI, H-ARS and lung, heart, respectively) approaches to understand selected doseand time-dependent organ injury within the acute radiation-induced ARS and DEARE (Farese et al. 2012; Jackson et al. 2012, 2014; MacVittie et al. 2012b; Garofalo et al. 2014; Medhora et al. 2015; Plett et al. 2015; Thrall et al. 2015, 2019). The models are:
An Evaluation of Biometric Monitoring Technologies for Vital Signs in the Era of COVID‐19

The novel coronavirus disease 2019 (COVID‐19) global pandemic has shifted how many patients receive outpatient care. Telehealth and remote monitoring have become more prevalent, and measurements taken in a patient’s home using biometric monitoring technologies (BioMeTs) offer convenient opportunities to collect vital sign data. Healthcare providers may lack prior experience using BioMeTs in remote patient care, and, therefore, may be unfamiliar with the many versions of BioMeTs, novel data collection protocols, and context of the values collected. To make informed patient care decisions based on the biometric data collected remotely, it is important to understand the engineering solutions embedded in the products, data collection protocols, form factors (physical size and shape), data quality considerations, and availability of validation information. This article provides an overview of BioMeTs available for collecting vital signs (temperature, heart rate, blood pressure, oxygen saturation, and respiratory rate) and discusses the strengths and limitations of continuous monitoring. We provide considerations for remote data collection and sources of validation information to guide BioMeT use in the era of COVID‐19 and beyond.
Mesoporous Silica Nanoparticles in Bioimaging

A biomedical contrast agent serves to enhance the visualisation of a specific (potentially targeted) physiological region. In recent years, mesoporous silica nanoparticles (MSNs) have developed as a flexible imaging platform of tuneable size/morphology, abundant surface chemistry, biocompatibility and otherwise useful physiochemical properties. This review discusses MSN structural types and synthetic strategies, as well as methods for surface functionalisation. Recent applications in biomedical imaging are then discussed, with a specific emphasis on magnetic resonance and optical modes together with utility in multimodal imaging.
Who Reads Food Labels? Selected Predictors of Consumer Interest in Front-of-Package and Back-of-Package Labels during and after the Purchase

The paper aims to identify selected predictors of food label use to extend our knowledge about consumer behavior related to food purchases. Two types of information were examined: front-of-package (FOP) and back-of-package (BOP), and two contexts of reading labels were distinguished: during shopping and at home. Various types of potential predictors were tested, including demographic (e.g., age, gender, household size, place of living), socioeconomic (e.g., education, professional activity, income), behavioral (e.g., purchasing certain types of products), and psychographic (e.g., importance attached to various types of information) criteria. The survey was conducted with the use of the CAWI (Computer-Assisted Web Interviews) methodology in a sample of 1051 Polish consumers. Quota sampling was applied based on sex, age, education, place of living (urban vs. rural), and region. Descriptive statistics, t-tests, ANOVAs, Pearson correlation coefficients, and multiple and retrograde step regressions were applied. In retrograde step regression models, only one predictor (self-rated knowledge about nutrition healthiness) turned out to be significant for all four measures of label reading. The remaining predictors were specific to selected measures of reading labels. The importance of the information about the content of fat and that about the health effects of consuming a food product were significant predictors of three types of food label use. This study confirms the necessity to investigate reading labels in fine-grained models, adapted to different types of labels and different contexts of reading. Our results show that demographic or socioeconomic variables are not significant predictors of reading food labels for a large group of Polish consumers.
Isoliquiritigenin Derivatives Inhibit RANKL-Induced Osteoclastogenesis by Regulating p38 and NF-κB Activation in RAW 264.7 Cells

Bone diseases may not be imminently life-threatening or a leading cause of death such as heart diseases or cancers. However, as aging population grows in almost every part of the world, they surely impose significant socioeconomic burden on the society, not to mention the patients and their families. Osteoporosis is the most common type of bone disease, which frequently develops in seniors, especially in postmenopausal women. Although currently several anti-osteoclastic drugs designed to suppress excessive osteoclast activation, a major cause of osteoporosis, are commercially available, accompanying adverse effects ranging from mild to severe have been reported as well. Natural products have become increasingly popular because of their effectiveness with fewer side effects. Isoliquiritigenin (ILG), a natural flavonoid from licorice, has been reported to suppress osteoclast differentiation and activation. In the present study, newly synthesized ILG derivatives were screened for their anti-osteoporotic activity as more potent substitute candidates to ILG. Out of the 12 ILG derivatives tested, two compounds demonstrated significantly improved bone loss in vitro by inhibiting both osteoclastogenesis and osteoclast activity. The results of the present study indicate that these compounds may serve as a potential drug for osteoporosis and warrant further studies to evaluate their in vivo efficacy.
MicroRNA miR-181—A Rheostat for TCR Signaling in Thymic Selection and Peripheral T-Cell Function

The selection of T cells during intra-thymic d evelopment is crucial to obtain a functional and simultaneously not self-reactive peripheral T cell repertoire. However, selection is a complex process dependent on T cell receptor (TCR) thresholds that remain incompletely understood. In peripheral T cells, activation, clonal expansion, and contraction of the active T cell pool, as well as other processes depend on TCR signal strength. Members of the microRNA (miRNA) miR-181 family have been shown to be dynamically regulated during T cell development as well as dependent on the activation stage of T cells. Indeed, it has been shown that expression of miR-181a leads to the downregulation of multiple phosphatases, implicating miR-181a as ‘‘rheostat’’ of TCR signaling. Consistently, genetic models have revealed an essential role of miR-181a/b-1 for the generation of unconventional T cells as well as a function in tuning TCR sensitivity in peripheral T cells during aging. Here, we review these broad roles of miR-181 family members in T cell function via modulating TCR signal strength.
Multiplicity-weighted Euler’s formula for symmetrically arranged space-filling polyhedra

For many tested cases of identical space-filling polyhedra, such as the space-group-specific asymmetric units or Dirichlet domains, the numbers of their faces (Fn), edges (En) and vertices (Vn), in each case normalized by division by the multiplicity of their (potentially special) symmetry position, fulfill a modified Euler’s formula Fn − En + Vn = 1.
Molecular and Therapeutic Aspects of Hyperbaric Oxygen Therapy in Neurological Conditions

In hyperbaric oxygen therapy (HBOT), the subject is placed in a chamber containing 100% oxygen gas at a pressure of more than one atmosphere absolute. This treatment is used to hasten tissue recovery and improve its physiological aspects, by providing an increased supply of oxygen to the damaged tissue. In this review, we discuss the consequences of hypoxia, as well as the molecular and physiological processes that occur in subjects exposed to HBOT. We discuss the efficacy of HBOT in treating neurological conditions and neurodevelopmental disorders in both humans and animal models. We summarize by discussing the challenges in this field, and explore future directions that will allow the scientific community to better understand the molecular aspects and applications of HBOT for a wide variety of neurological conditions.
The Impact of Educative News Articles about Suicide Prevention: A Randomized Controlled Trial

ABSTRACT Media stories featuring stories of personal experiences of coping with suicidal ideation have been shown to decrease suicide risk, but it is unclear whether more impersonal awareness materials have similar effects. This study aimed to test the impact of impersonal educative news articles featuring interviews with suicide prevention experts. Because the impact of news articles may be determined by the articles’ pull quotes and headlines, we also aimed to compare the impact of two versions of the same suicide prevention news article. One version featured headlines and pull quotes highlighting the message that suicide is preventable, whereas the other version focused on the message that suicide is prevalent. In a web-based randomized controlled trial, n = 425 participants either read a news article featuring a prevention expert with one of the above versions of the same text or an article unrelated to suicide. Data on suicidal ideation, stigmatizing attitudes toward suicidal individuals, policy attitudes toward suicide prevention, help-seeking intentions, and assumptions on the prevalence of suicide-related behavior were measured with questionnaires. The assumed prevalence of suicide in the population was greater in both intervention groups than in the control group, but the articles did not have an impact on other outcomes, and there were no differences for variations in headlines and pull quotes. Impersonal suicide prevention articles appear safe to use and do not have an impact on suicide risk factors in general population samples.
Cancer Therapy; Prospects for Application of Nanoparticles for Magnetic-Based Hyperthermia

Abstract Hyperthermic therapy is defined as increasing the temperature of tumor tissues to 40–43 °C that has been effective approach for destroying malignant cells in the field of cancer therapy. Recent line of research has applied different approaches along with hyperthermic treatment to obtain high efficiency and little side effects. Magnetic nanoparticle-based hyperthermia has demonstrated an improved functionality in targeting malignant cells and implement their therapeutic role by heating the tumor cells. Here in this review article, we clarify the diverse aspects of magnetic nanoparticles in the treatment of cancer.
Canalization and Robustness in Human Genetics and Disease.

Canalization refers to the evolution of populations such that the number of individuals who deviate from the optimum trait, or experience disease, is minimized. In the presence of rapid cultural, environmental, or genetic change, the reverse process of decanalization may contribute to observed increases in disease prevalence. This review starts by defining relevant concepts, drawing distinctions between the canalization of populations and robustness of individuals. It then considers evidence pertaining to three continuous traits and six domains of disease. In each case, existing genetic evidence for genotype-by-environment interactions is insufficient to support a strong inference of decanalization, but we argue that the advent of genome-wide polygenic risk assessment now makes an empirical evaluation of the role of canalization in preventing disease possible. Finally, the contributions of both rare and common variants to congenital abnormality and adult onset disease are considered in light of a new kerplunk model of genetic effects. Expected final online publication date for the Annual Review of Genetics, Volume 54 is November 23, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Interpersonal Synchronization Processes in Discrete and Continuous Tasks

Abstract Three frameworks have been proposed to account for interpersonal synchronization: The information processing approach argues that synchronization is achieved by mutual adaptation, the coordination dynamics perspective supposes a continuous coupling between systems, and complexity matching suggests a global, multi-scale interaction. We hypothesized that the relevancy of these models was related to the nature of the performed tasks. 10 dyads performed synchronized tapping and synchronized forearm oscillations, in two conditions: full (participants had full information about their partner), and digital (information was limited to discrete auditory signals). Results shows that whatever the task and the available information, synchronization was dominated by a discrete mutual adaptation. These results question the relevancy of the coordination dynamics perspective in interpersonal coordination.
Theoretical evaluation of graphene quantum dots on DNA genotoxicity: a combination of density functional theory and molecular dynamics simulation.

Owing to unique morphology, ultra-small lateral sizes and exceptional properties, graphene quantum dots (GQDs) hold great potential in many applications, especially in the field of electrochemical biosensors, bioimaging, drug delivery, gene delivery etc. Its biosafety and potential genotoxicity to human and animal cells is a growing concern in recent years. Especially, the potential DNA damaging of GQDs is very important but still unclear. In this study, the effect of GQDs on DNA damaging has been evaluated by a combination of molecular dynamics simulation and density functional theory. Our results demonstrates that the DNA damaging mechanism of GQDs depends on the size of GQDs. The small GQDs (7 benzene rings) tends to insert into the inner of DNA molecules and make the base mismatch of DNA. The relative large GQDs (61 benzene rings) tends to absorb on two ends of DNA molecule and make DNA unwinding. Due to the strong absorption between guanine (G) and GQDs, the effect of GQDs is much larger on G than other three bases (A, C and T). In addition, the concentration of GQDs could also affect the results of DNA damaging.
Omega-3 Polyunsaturated Fatty Acids EPA and DHA as an Adjunct to Non-Surgical Treatment of Periodontitis: A Randomized Clinical Trial

Periodontitis is a chronic multifactorial inflammatory disease that leads to the loss of supportive tissues around the teeth with gradual deterioration of masticatory function and esthetics, resulting eventually in the decrease of the life quality. Host immune response triggered by bacterial biofilm is responsible for the chronic periodontal inflammation and ongoing tissue loss. Omega-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory properties, thus may be used for the treatment of chronic inflammatory diseases. In this study, we aimed to evaluate the effect of dietary supplementation with omega-3 PUFA in the patients with stage III and IV periodontitis. Thirty otherwise healthy patients were treated with scaling and root planning (SRP). In the test group (n = 16), patients were additionally supplemented with 2.6 g of EPA and 1.8 g of DHA. In the control group (n = 14), patients received only SRP. Periodontal examination was performed at baseline and three months following initial therapy. Salivary samples were taken twice at baseline and at the end of the experiment. We found that there was a statistically significant reduction in the bleeding on probing (BOP) and improvement of clinical attachment loss (CAL) at three months in the test group compared to the control group. Moreover, a statistically significant higher percentage of closed pockets (probing depth ≤ 4 mm without BOP) was achieved in the test group vs. control group after three months of treatment. Accordingly, the levels of pro-inflammatory cytokines/chemokines interleukin (IL)-8 and IL-17 were markedly lower, while the level of anti-inflammatory IL-10 was significantly higher in the salivary samples of the patients supplemented with omega-3 PUFA at three months in comparison to the patients treated with SRP alone. Our findings demonstrate that dietary intervention with high-dose of omega-3 PUFA during non-surgical therapy may have potential benefits in the management of periodontitis.
Hypermethylation status of DAPK, MGMT and RUNX3 in HPV negative oral and oropharyngeal squamous cell carcinoma

Abstract Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR. Hypermethylation frequencies found for DAPK, MGMT and RUNX3 were 38.88%, 19.44% and 1.38% respectively. Patients with MGMT hypermethylation had a better 2-year overall survival compared to patients without methylation. Being MGMT a repair gene for alkylating agents, it could be a biomarker of treatment response for patients who are candidates for cisplatin chemotherapy, predicting drug resistance. In view of the considerable levels of hypermethylation in cancer cells and, for MGMT, its prognostic relevance, DAPK and MGMT show potential as epigenetic markers, in a way that additional studies may test its viability and efficacy in clinical management.
Weak binding to the A2RE RNA rigidifies hnRNPA2 RRMs and reduces liquid–liquid phase separation and aggregation

Abstract hnRNPA2 is a major component of mRNA transport granules in oligodendrocytes and neurons. However, the structural details of how hnRNPA2 binds the A2 recognition element (A2RE) and if this sequence stimulates granule formation by enhancing phase separation of hnRNPA2 has not yet been studied. Using solution NMR and biophysical studies, we find that each of the two individual RRMs retain the domain structure observed in complex with RNA but are not rigidly confined (i.e. they move independently) in solution in the absence of RNA. hnRNPA2 RRMs bind the minimal rA2RE11 weakly but at least, and most likely, two hnRNPA2 molecules are able to simultaneously bind the longer 21mer myelin basic protein A2RE. Upon binding of the RNA, NMR chemical shift deviations are observed in both RRMs, suggesting both play a role in binding the A2RE11. Interestingly, addition of short A2RE RNAs or longer RNAs containing this sequence completely prevents in vitro phase separation of full-length hnRNPA2 and aggregation of the disease-associated mutants. These findings suggest that RRM interactions with specific recognition sequences alone do not account for nucleating granule formation, consistent with models where multivalent protein:RNA and protein:protein contacts form across many sites in granule proteins and long RNA transcripts.