Miracle-dz/UniFAR-FTUs huggingface dataset:
pH‐dependent conformational dynamics of beta‐secretase 1: A molecular dynamics study

Beta‐secretase 1 (BACE‐1) is an aspartyl protease implicated in the overproduction of β‐amyloid fibrils responsible for Alzheimer disease. The process of β‐amyloid genesis is known to be pH dependent, with an activity peak between solution pH of 3.5 and 5.5. We have studied the pH‐dependent dynamics of BACE‐1 to better understand the pH dependent mechanism. We have implemented support for graphics processor unit (GPU) accelerated constant pH molecular dynamics within the AMBER molecular dynamics software package and employed this to determine the relative population of different aspartyl dyad protonation states in the pH range of greatest β‐amyloid production, followed by conventional molecular dynamics to explore the differences among the various aspartyl dyad protonation states. We observed a difference in dynamics between double‐protonated, mono‐protonated, and double‐deprotonated states over the known pH range of higher activity. These differences include Tyr 71‐aspartyl dyad proximity and active water lifetime. This work indicates that Tyr 71 stabilizes catalytic water in the aspartyl dyad active site, enabling BACE‐1 activity.
Analysis of Different Parameters Affecting Diffusion, Propagation and Survival of Staphylophages in Bacterial Biofilms

The elimination of bacterial biofilms remains a major challenge due to their recalcitrant nature. Bacteriophages, viruses that infect bacteria, have been gaining increasing attention as biofilm control agents. However, the development of a successful phage-based strategy requires in-depth analysis of different parameters. It is particularly important to determine the ability of a given phage to diffuse, propagate and remain viable within the complex biofilm structure. Here, we examine some of these properties for two staphylophages, vB_SauM_phiIPLA-RODI and vB_SepM_phiIPLA-C1C. Both Staphylococcus aureus and Staphylococcus epidermidis are important opportunistic pathogens that readily form biofilms on a wide array of biotic and abiotic surfaces. Our results confirmed that both phages could penetrate through biofilms formed by several bacterial strains with varying degrees of susceptibility to the viruses and biofilm-forming abilities. However, phage penetration differed depending on the specific bacterium or combination of bacteria. The data presented here suggest that the factors determining the diffusion rate of phages in biofilms include the amount of attached biomass, susceptibility of the strain, initial phage titer, phage entrapment in the extracellular matrix, and phage inactivation. This information will help to further characterize phage-bacteria interactions within biofilm communities and will be valuable for the development of antistaphylococcal products based on these phages.
A Semi-Empirical Performance Study of Two-Hop DSRC Message Relaying at Road Intersections

This paper is focused on a vehicle-to-vehicle (V2V) communication system operating at a road intersection, where the communication links can be either line-of-sight (LOS) or non-line-of-sight (NLOS). We present a semi-empirical analysis of the packet delivery ratio of dedicated short-range communication (DSRC) safety messages for both LOS and NLOS scenarios using a commercial transceiver. In a NLOS scenario in which the reception of a safety message may be heavily blocked by concrete buildings, direct communication between the on-board units (OBUs) of vehicles through the IEEE 802.11p standard tends to be unreliable. On the basis of the semi-empirical result of safety message delivery at an intersection, we propose two relaying mechanisms (namely, simple relaying and network-coded relaying) via a road-side unit (RSU) to improve the delivery ratio of safety messages. Specifically, we designed RSU algorithms to optimize the number of relaying messages so as to maximize the message delivery ratio of the entire system in the presence of data packet collisions. Numerical results show that our proposed relaying schemes lead to a significant increase in safety message delivery rates.
Antiviral Activity of Tannic Acid Modified Silver Nanoparticles: Potential to Activate Immune Response in Herpes Genitalis

(1) Background: Tannic acid is a plant-derived polyphenol showing antiviral activity mainly because of an interference with the viral adsorption. In this work, we tested whether the modification of silver nanoparticles with tannic acid (TA-AgNPs) can provide a microbicide with additional adjuvant properties to treat genital herpes infection. (2) Methods: The mouse model of the vaginal herpes simplex virus 2 (HSV-2) infection was used to test immune responses after treatment of the primary infection with TA-AgNPs, and later, after a re-challenge with the virus. (3) Results: The mice treated intravaginally with TA-AgNPs showed better clinical scores and lower virus titers in the vaginal tissues soon after treatment. Following a re-challenge, the vaginal tissues treated with TA-AgNPs showed a significant increase in the percentages of IFN-gamma+ CD8+ T-cells, activated B cells, and plasma cells, while the spleens contained significantly higher percentages of IFN-gamma+ NK cells and effector-memory CD8+ T cells in comparison to NaCl-treated group. TA-AgNPs-treated animals also showed significantly better titers of anti-HSV-2 neutralization antibodies in sera; and (4) Conclusions: Our findings suggest that TA-AgNPs sized 33 nm can be an effective anti-viral microbicide to be applied upon the mucosal tissues with additional adjuvant properties enhancing an anti-HSV-2 immune response following secondary challenge.
Preschoolers Understand the Moral Dimension of Factual Claims

Research on children’s developing moral cognition has mostly focused on their evaluation of, and reasoning about, others’ intrinsically harmful (non-)verbal actions (e.g., hitting, lying). But assertions may have morally relevant (intended or unintended) consequences, too. For instance, if someone wrongly claims that “This water is clean! ,” such an incorrect representation of reality may have harmful consequences to others. In two experiments, we investigated preschoolers’ evaluation of others’ morally relevant factual claims. In Experiment 1, children witnessed a puppet making incorrect assertions that would lead to harm or to no harm. In Experiment 2, incorrect assertions would always lead to harm, but the puppet either intended the harm to occur or not. Children evaluated the puppet’s factual claim more negatively when they anticipated harmful versus harmless consequences (Experiment 1) and when the puppet’s intention was bad versus good over and above harmful consequences (Experiment 2). These findings suggest that preschoolers’ normative understanding is not limited to evaluating others’ intrinsically harmful transgressions but also entails an appreciation of the morally relevant consequences of, and intentions underlying, others’ factual claims.
T-cell receptor-α repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing

Alloreactivity or opportunistic infections following allogeneic stem cell transplantation are difficult to predict and contribute to post-transplantation mortality. How these immune reactions result in changes to the T-cell receptor repertoire remains largely unknown. Using next-generation sequencing, the T-cell receptor alpha (TRα) repertoire of naïve and memory CD8+ T cells from 25 patients who had received different forms of allogeneic transplantation was analyzed. In parallel, reconstitution of the CD8+/CD4+ T-cell subsets was mapped using flow cytometry. When comparing the influence of anti-T-cell therapy, a delay in the reconstitution of the naïve CD8+ T-cell repertoire was observed in patients who received in vivo T-cell depletion using antithymocyte globulin or post-transplantation cyclophosphamide in case of haploidentical transplantation. Sequencing of the TRα identified a repertoire consisting of more dominant clonotypes (>1% of reads) in these patients at 6 and 18 months post transplantation. When comparing donor and recipient, approximately 50% and approximately 80% of the donors’ memory repertoire were later retrieved in the naïve and memory CD8+ T-cell receptor repertoire of the recipients, respectively. Although there was a remarkable expansion of single clones observed in the recipients’ memory CD8+ TRα repertoire, no clear association between graft-versus-host disease or cytomegalovirus infection and T-cell receptor diversity was identified. A lower TRα diversity was observed in recipients of a cytomegalovirus-seropositive donor (P=0.014). These findings suggest that CD8+ T-cell reconstitution in transplanted patients is influenced by the use of T-cell depletion or immunosuppression and the donor repertoire.
Relevance of MicroRNAs as Potential Diagnostic and Prognostic Markers in Colorectal Cancer

Colorectal cancer (CRC) is currently the third and the second most common cancer in men and in women, respectively. Every year, more than one million new CRC cases and more than half a million deaths are reported worldwide. The majority of new cases occur in developed countries. Current screening methods have significant limitations. Therefore, a lot of scientific effort is put into the development of new diagnostic biomarkers of CRC. Currently used prognostic markers are also limited in assessing the effectiveness of CRC therapy. MicroRNAs (miRNAs) are a promising subject of research especially since single miRNA can recognize a variety of different mRNA transcripts. MiRNAs have important roles in epigenetic regulation of basic cellular processes, such as proliferation, apoptosis, differentiation, and migration, and may serve as potential oncogenes or tumor suppressors during cancer development. Indeed, in a large variety of human tumors, including CRC, significant distortions in miRNA expression profiles have been observed. Thus, the use of miRNAs as diagnostic and prognostic biomarkers in cancer, particularly in CRC, appears to be an inevitable consequence of the advancement in oncology and gastroenterology. Here, we review the literature to discuss the potential usefulness of selected miRNAs as diagnostic and prognostic biomarkers in CRC.
Trading information complexity for error II

Consider the standard two-party communication model. This paper, follows up [DFHL18], studies the dependency of information complexity on error allowed to compute a function. Two of our main results on prior-free information complexity are: • For both internal and external information complexity, we show to compute any function with error 1/2 − ǫ, at least Ω(ǫ) and at most O(ǫ) information must be revealed. Both bounds are tight via examples from [BM13]. • For external information complexity, we show to compute any function with small error ǫ > 0, one can save external information cost, against computing the function without zero, at least Ω(ǫ) and at most O(h( √ ǫ)) where h(·) is the binary entropy function. We do not know either of them is tight. However, when we consider prior-free external information complexity over only product distributions, the lower bound can be improved to Ω(h(ǫ)), with a simpler proof than the one in [DFHL18].
The Mediating Role of Perceived Social Support in the Relationships Between General Causality Orientations and Locus of Control With Psychopathological Symptoms

The main aim of this study is to investigate the mediator role of perceived social support in the relationship between general causality orientations and locus of control with psychopathological symptoms. Total 751 participants were consisted of 558 female ages between 17 and 36 (Female M = 19.03, SD = 0.09) (74.3%), 192 male ages between 17 and 37 (Male M = 20.71, SD = 0.17) (25.6%) and a participant who did not provide any gender information. We used the General Causality Orientations Scale (GCOS) and Locus of Control Scale (LOCS) in order to understand the basic motivation for the emergence of behavior. Beck depression Inventory (BDI) used to evaluate the psychological symptoms for depression, Maudsley Obsessive Compulsive Inventory (MOCI) for obsessive-compulsive symptomology and Brief Symptom Inventory (BSI) for overall psychological distress and finally to evaluate mediating role of social support used the Perceived Social Support Scale (PSSS). According to the results, having internal locus of control and autonomy orientation have shown positive effect to statistically significant predictors for psychological symptomology, having external locus of control and impersonal orientation have shown negative effect. Perceived social support was found to be suited for the role of partial mediator, and social support from friends was found to have more positive roles than social support from family. In conclusion, exceedingly considerable to conduct further research in order to contribute to the understanding of the mediating role of general causality orientations and locus of control with psychopathology symptomology.
Transgenerational transmission of maternal stimulatory experience in domesticated birds

The environmental stimuli experienced by a female can influence phenotypes and gene expression in the subsequent generations. We used a specifically designed domesticated‐bird model to examine the transgenerational transmission of maternal stimulus exposure, a phenomenon that has been observed but has not been understood in noninbred animals. We subjected parental generation [filial (F)0] hens to viral‐ or bacterial‐like stimulation after artificial insemination. Subsequent filial generations F1 and F2 transmitted growth or fertility variations without further stimulation in contrast to the controls. The whole‐genome bisulfite sequence and next‐generation mRNA sequencing of peripheral blood lymphocytes (PBLs) from the F1 generation revealed DNA methylome and transcriptome differences in the F1 polyriboinosinic:polyribocytidylic [poly(I:C)] acid or LPS offspring, compared with the F1 controls. In the F1 offspring, DNA methylation changes induced by maternal immune stimulation may have contributed to transcriptional variation. Pathways analysis indicated that the metabolic processes of xenobiotics and drug metabolism pathways, as well as reproduction‐related pathways, were involved in the transgenerational transmission of maternal stimulatory experience. Furthermore, LPS‐induced transcriptional transmission may have contributed to subfertility, as indicated by the results of comparative analysis between the transcriptomes of spleen tissues across the F0 and F1 generations, as well as the correlative analysis between the transcriptome and reproductive phenotypes. Our findings provide a framework for determining the mechanisms by which maternal stimulatory factors can be inherited transgenerationally with respect to growth, fertility, DNA methylation, and transcriptional levels in outbred animals. —Liu, L. , Yang, N. , Xu, G. , Liu, S. , Wang, D. , Song, J., Duan, Z. , Yang, S. , Yu, Y. Transgenerational transmission of maternal stimulatory experience in domesticated birds. FASEB J. 32, 7002–7017 (2018). www.fasebj. org
Sextortion Among Adolescents: Results From a National Survey of U.S. Youth

Sextortion is the threatened dissemination of explicit, intimate, or embarrassing images of a sexual nature without consent, usually for the purpose of procuring additional images, sexual acts, money, or something else. Despite increased public interest in this behavior, it has yet to be empirically examined among adolescents. The current study fills this gap by exploring the prevalence of sextortion behaviors among a nationally representative sample of 5,568 U.S. middle and high school students. Approximately 5% of students reported that they had been the victim of sextortion, while about 3% admitted to threatening others who had shared an image with them in confidence. Males and nonheterosexual youth were more likely to be targeted, and males were more likely to target others. Moreover, youth who threatened others with sextortion were more likely to have been victims themselves. Implications for future research, as well as the preventive role that youth-serving professionals can play, are discussed.
The Predictive Value of Plasma Brain Natriuretic Peptide and Galectin-3 in Elderly Patients Admitted for Heart Failure †

Galectin-3 is demonstrated to be a robust independent marker of cardiovascular mid-term (18-month) outcomes in heart failure (HF) patients. The aim of this study was to analyze the value of a pre-discharged determination of galectin-3 alone and with brain natriuretic peptide (BNP) in predicting mid-term outcomes in elderly patients (>70 years old) discharged after an acute decompensated HF (ADHF) episode. Methods: all elderly (≥70 years old) HF subjects discharged alive after an ADHF were enrolled. All patients underwent a determination of BNP and galectin-3, a 6-min walking test (6MWT), and an echocardiogram within 48 h of hospital discharge. Cardiac death, cardiac transplantation, and worsening heart failure requiring readmission to hospital were considered cardiovascular events. Results: 84 patients (63 males (75%), age 77.5 ± 5.9 years old) were analyzed (mean follow-up: 16.2 ± 12.3 months). During the follow-up, 45 events (53.6%) were scheduled (18 cardiac deaths, 27 re-hospitalizations for ADHF). HF patients who suffered an event demonstrated more impaired ventricular function (p = 0.04), higher value of BNP (p = 0.02), and Gal-3 at a pre-discharge evaluation (p = 0.05). By choosing adequate cut-off points (BNP ≥ 500 pg/mL and Gal-3 ≥ 17.6 ng/mL), the Kaplan–Meier curves depicted a powerful stratification using Galectin-3 > 17.6 ng/mL alone (log-rank 13.22; p = 0.0003), and by adding BNP + Gal-3, an even better result was obtained (log-rank 17.96; p < 0.00001). Conclusion: in an elderly population, by adding Gal-3 to BNP, a single pre-discharge strategy testing seemed to obtain a satisfactorily predictive value in alive HF patients discharged after an ADHF episode.
A systematic performance evaluation of clustering methods for single-cell RNA-seq data

Subpopulation identification, usually via some form of unsupervised clustering, is a fundamental step in the analysis of many single-cell RNA-seq data sets. This has motivated the development and application of a broad range of clustering methods, based on various underlying algorithms. Here, we provide a systematic and extensible performance evaluation of 14 clustering algorithms implemented in R, including both methods developed explicitly for scRNA-seq data and more general-purpose methods. The methods were evaluated using nine publicly available scRNA-seq data sets as well as three simulations with varying degree of cluster separability. The same feature selection approaches were used for all methods, allowing us to focus on the investigation of the performance of the clustering algorithms themselves. We evaluated the ability of recovering known subpopulations, the stability and the run time and scalability of the methods. Additionally, we investigated whether the performance could be improved by generating consensus partitions from multiple individual clustering methods. We found substantial differences in the performance, run time and stability between the methods, with SC3 and Seurat showing the most favorable results. Additionally, we found that consensus clustering typically did not improve the performance compared to the best of the combined methods, but that several of the top-performing methods already perform some type of consensus clustering. All the code used for the evaluation is available on GitHub ( https://github.com/markrobinsonuzh/scRNAseq_clustering_comparison). In addition, an R package providing access to data and clustering results, thereby facilitating inclusion of new methods and data sets, is available from Bioconductor ( https://bioconductor.org/packages/DuoClustering2018).
Protein token: a dynamic unit in protein interactions.

In this study, we introduced a new unit, named "protein token", as a dynamic protein structural unit for protein-protein interactions. Unlike the conventional structural units, protein token is not based on the sequential or spatial arrangement of residues, but comprises remote residues involved in cooperative conformational changes during protein interactions. Application of protein token on Ras GTPases revealed various tokens present in the superfamily. Distinct token combinations were found in H-Ras interacting with its various regulators and effectors, directing to a possible clue for the multiplexer property of Ras superfamily. Thus, this protein token theory may provide a new approach to study protein-protein interactions in broad applications.
Prospects for circadian treatment of mood disorders

Abstract Disruption of circadian clocks is strongly associated with mood disorders. Chronotherapies targeting circadian rhythms have been shown to be very effective treatments of mood disorders, but still are not widely used in clinical practice. The mechanisms by which circadian disruption leads to mood disorders are poorly characterized and, therefore, may not convince clinicians to apply chronotherapies. Hence, in this review, we describe specific potential mechanisms, in order to make this connection more credible to clinicians. We believe that four major features of disrupted clocks may contribute to the development of mood disorders: (1) loss of synchronization to environmental 24-h rhythms, (2) internal desynchronization among body clocks, (3) low rhythm amplitude, and (4) changes in sleep architecture. Discussing these attributes and giving plausible examples, we will discuss prospects for relatively simple chronotherapies addressing these features that are easy to implement in clinical practice. Key messages In this review, we describe specific potential mechanisms by which disrupted clocks may contribute to the development of mood disorders: (1) loss of synchronization to environmental 24-h rhythms, (2) internal desynchronization among body clocks, (3) low rhythm amplitude, and (4) changes in sleep architecture. We provide prospects for relatively simple chronotherapies addressing these features that are easy to implement in clinical practice.
Comment on “DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification”

Chen et al. (Reports, 17 February 2017, p. 752) highlight an important problem of sequencing artifacts caused by DNA damage at the time of sample processing. However, their manuscript contains several errors that led the authors to incorrect conclusions. Moreover, the same sequencing artifacts were previously described and mitigated in The Cancer Genome Atlas and other published sequencing projects.
Solidarity and Care as Relational Practices

Many working in bioethics today are engaging in forms of normative interpretation concerning the meaningful contexts of relational agency and institutional structures of power. Using the framework of relational bioethics, this article focuses on two significant social practices that are significant for health policy and public health: the practices of solidarity and the practices of care. The main argument is that the affirming recognition of, and caring attention paid to, persons as moral subjects can politically motivate a society in three respects. The recognition of solidarity and the attention of care can prompt progressive change toward a democratic willingness: (a) to provide for equal respect for rights and dignity; (b) to provide the social resources and services needed for just health and well-being; and (c) to focus its creativity and wealth on the actualization of potential flourishing of each and all. Solidarity is discussed as a morally developmental stance that moves from standing up for another, standing up with another, and standing up as another. Care is discussed as a morally developmental stance that moves from the attentive rehabilitation of another, attentive companionship with and for another, and attentive commitment to another.