Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional Regulation in Ebola Virus: Effects of Gene Border Structure and Regulatory Elements on Gene Expression and Polymerase Scanning Behavior

ABSTRACT The highly pathogenic Ebola virus (EBOV) has a nonsegmented negative-strand (NNS) RNA genome containing seven genes. The viral genes either are separated by intergenic regions (IRs) of variable length or overlap. The structure of the EBOV gene overlaps is conserved throughout all filovirus genomes and is distinct from that of the overlaps found in other NNS RNA viruses. Here, we analyzed how diverse gene borders and noncoding regions surrounding the gene borders influence transcript levels and govern polymerase behavior during viral transcription. Transcription of overlapping genes in EBOV bicistronic minigenomes followed the stop-start mechanism, similar to that followed by IR-containing gene borders. When the gene overlaps were extended, the EBOV polymerase was able to scan the template in an upstream direction. This polymerase feature seems to be generally conserved among NNS RNA virus polymerases. Analysis of IR-containing gene borders showed that the IR sequence plays only a minor role in transcription regulation. Changes in IR length were generally well tolerated, but specific IR lengths led to a strong decrease in downstream gene expression. Correlation analysis revealed that these effects were largely independent of the surrounding gene borders. Each EBOV gene contains exceptionally long untranslated regions (UTRs) flanking the open reading frame. Our data suggest that the UTRs adjacent to the gene borders are the main regulators of transcript levels. A highly complex interplay between the different cis-acting elements to modulate transcription was revealed for specific combinations of IRs and UTRs, emphasizing the importance of the noncoding regions in EBOV gene expression control. IMPORTANCE Our data extend those from previous analyses investigating the implication of noncoding regions at the EBOV gene borders for gene expression control. We show that EBOV transcription is regulated in a highly complex yet not easily predictable manner by a set of interacting cis-active elements. These findings are important not only for the design of recombinant filoviruses but also for the design of other replicon systems widely used as surrogate systems to study the filovirus replication cycle under low biosafety levels. Insights into the complex regulation of EBOV transcription conveyed by noncoding sequences will also help to interpret the importance of mutations that have been detected within these regions, including in isolates of the current outbreak.
Endothelium‐specific CYP2J2 overexpression attenuates age‐related insulin resistance

Ample evidences demonstrate that cytochrome P450 epoxygenase‐derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti‐inflammatory, and cardiovascular protective effects. In this study, we investigated the effects of endothelium‐specific CYP2J2 overexpression on age‐related insulin resistance and metabolic dysfunction. Endothelium‐specific targeting of the human CYP epoxygenase, CYP2J2, transgenic mice (Tie2‐CYP2J2‐Tr mice) was utilized. The effects of endothelium‐specific CYP2J2 overexpression on aging‐associated obesity, inflammation, and peripheral insulin resistance were evaluated by assessing metabolic parameters in young (3 months old) and aged (16 months old) adult male Tie2‐CYP2J2‐Tr mice. Decreased insulin sensitivity and attenuated insulin signaling in aged skeletal muscle, adipose tissue, and liver were observed in aged adult male mice, and moreover, these effects were partly inhibited in 16‐month‐old CYP2J2‐Tr mice. In addition, CYP2J2 overexpression‐mediated insulin sensitization in aged mice was associated with the amelioration of inflammatory state. Notably, the aging‐associated increases in fat mass and adipocyte size were only observed in 16‐month‐old wild‐type mice, and CYP2J2 overexpression markedly prevented the increase in fat mass and adipocyte size in aged Tie2‐CYP2J2‐Tr mice, which was associated with increased energy expenditure and decreased lipogenic genes expression. Furthermore, these antiaging phenotypes of Tie2‐CYP2J2‐Tr mice were also associated with increased muscle blood flow, enhanced active‐phase locomotor activity, and improved mitochondrial dysfunction in skeletal muscle. Collectively, our findings indicated that endothelium‐specific CYP2J2 overexpression alleviated age‐related insulin resistance and metabolic dysfunction, which highlighted CYP epoxygenase‐EET system as a potential target for combating aging‐related metabolic disorders.
Letter: Regulating Hypothalamus Gene Expression in Food Intake: Dietary Composition or Calorie Density? (Diabetes Metab J 2017;41:121-7)

Corresponding author: Bo Kyung Koo https://orcid.org/0000-0002-6489-2656 Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea E-mail: bokyungkoomd@gmail.com Jang et al. [1] reported that high saturated fatty acid (SFA) or n-3 polyunsaturated fat acid (PUFA) increased proopiomelanocortin (POMC) mRNA expression significantly compared with baseline. The expression of POMC was more prominently increased in SFA compared with PUFA. However, compared with carbohydrate (CHO)-rich diet, even SFA-rich diet lead to a significantly lower level of POMC mRNA expression. In contrast, in the case of neuropeptide Y (NPY), the mRNA expression was significantly lower in CHO-rich diet compared with SFA or PUFA-rich diet. Although Jang et al. [1] mentioned that the evidence regarding direct effect of different fatty acid diets on satiety in hypothalamus is sparse, previous studies have consistently reported that PUFA increases POMC expression by G-protein-coupled receptor 40 [2,3]. In the case of SFA, even though SFA decreased NPY mRNA expression [4], SFA could not alter POMC expression level [4,5], which is opposite to study of Jang et al. [1] that claimed SFA increased POMC mRNA level more prominently compared with PUFA. They should address the controversy between the previous studies and theirs. In addition, there have been studies on the association between glucagon-like peptide-1 (GLP-1) and dietary macronutrient composition. As is already well known, GLP-1 affects food intake [6-8]. Fat-rich meal increased GLP-1 response more prominently compared with isocaloric CHO-rich meals in human [9]. In addition, dietary fat composition also affects GLP-1 response: unsaturated fatty acids increase GLP-1 more than SFA [10]. Considering that GLP-1 reduces food intake by directly stimulating POMC/cocaineand amphet amineregulated transcript (CART) neurons [6,7], there is a discrepancy between the previous studies [6,7] and find ings of Jang et al. [1] that showed CHO-rich meal and SFA increased POMC expression level more compared with PUFA. Along with POMC stimulation, GLP-1 can also affect NPY; it indirectly inhibits neurons expressing NPY and agouti-related peptide (AgRP) via γ-aminobutyric acid (GABA)-dependent signaling [6,7]. Hypothalamic NPY and AgRP mRNAs are significantly increased by fasting, which can be significantly attenuated by GLP-1 treatment [8]. Considering the different effect on GLP1 response according to dietary fatty acid composition, the effect of dietary fatty acid on POMC or NPY mRNA expression should be interpreted in terms of changes in GLP-1 level. Lastly, plasma glucose, free fatty acid, lipid, leptin, and ghrelin levels are very important factors in satiety regulation. I wonder if there were any differences in these levels in response to the interventions.
Shift-Life Interactive Art: Mixed-Reality Artificial Ecosystem Simulation

This article presents a detailed design, development, and implementation of a Mixed Reality Art-Science collaboration project which was exhibited during Darwin’s bicentenary exhibition at Shrewsbury, England. As an artist-led project the concerns of the artist were paramount, and this article presents Shift-Life as part of an ongoing exploration into the parallels between the nonlinear human thinking process and computation using semantic association to link items into ideas, and ideas into holistic concepts. Our art explores perceptions and states of mind as we move our attention between the simulated world of the computer and the real world we inhabit, which means that any viewer engagement is participatory rather than passive. From a Mixed Reality point of view, the lead author intends to explore the convergence of the physical and virtual, therefore the formalization of the Mixed Reality system, focusing on the integration of artificial life, ecology, physical sensors, and participant interaction through an interface of physical props. It is common for digital media artists to allow viewers to activate a work either through a computer screen via direct keyboard or mouse manipulation, or through immersive means. For “Shift-Life” the artist was concerned with a direct “relational” approach where viewers would intuitively engage with the installation’s everyday objects, and with each other, to fully experience the piece. The Mixed Reality system is mediated via physical environmental sensors, which affect the virtual environment and autonomous agents, which in turn reacts and is expressed as virtual pixels projected onto a physical surface. The tangible hands-on interface proved to be instinctive, attractive, and informative on many levels, delivering a good example of collaboration between the arts and science.
Comparison of Physiological and Psychological Relaxation Using Measurements of Heart Rate Variability, Prefrontal Cortex Activity, and Subjective Indexes after Completing Tasks with and without Foliage Plants

The objective of this study was to compare physiological and psychological relaxation by assessing heart rate variability (HRV), prefrontal cortex activity, and subjective indexes while subjects performed a task with and without foliage plants. In a crossover experimental design, 24 university students performed a task transferring pots with and without a foliage plant for 3 min. HRV and oxyhemoglobin (oxy-Hb) concentration in the prefrontal cortex were continuously measured. Immediately thereafter, subjective evaluation of emotions was performed using a modified semantic differential (SD) method and a profile of mood state questionnaire (POMS). Results showed that the natural logarithmic (ln) ratio of low frequency/high frequency, as an estimate of sympathetic nerve activity, was significantly lower while performing the task with foliage plants for the average 3 min measurement interval. Oxy-Hb concentration in the left prefrontal cortex showed a tendency to decrease in the 2–3 min interval in the task with foliage plants compared to the task without plants. Moreover, significant psychological relaxation according to POMS score and SD was demonstrated when the task involved foliage plants. In conclusion, the task involving foliage plants led to more physiological and psychological relaxation compared with the task without foliage plants.
Rotavirus Genomic RNA Complex Forms via Specific RNA–RNA Interactions: Disruption of RNA Complex Inhibits Virus Infectivity

Rotavirus (RV), a member of the Reoviridae family, causes infection in children and infants, with high morbidity and mortality. To be viable, the virus particle must package a set of eleven RNA segments. In order to understand the packaging mechanism, here, we co-synthesized sets of RNA segments in vitro in different combinations and detected by two alternate methods: the electrophoretic mobility shift assay (EMSA) and the RNA-bead pull-down assay. We showed that viral positive-sense RNA segments interact with each other in a specific manner, forming RNA complexes, and that the RNA–RNA interactions followed a sequential order initiated by small RV segments. Further, we demonstrated that RNA complexes were perturbed by targeted specific antisense oligoribonucleotides (ORNs) complementary to short RNA sequences, indicating that the RNA–RNA interactions between different segments were sequence-specific. The same inhibitory ORNs also had the capability to inhibit virus replication. The combined in vitro and in vivo data inferred that RNA–RNA interactions and specific complex formation are essential for sorting different segments, possibly prior to, or during, genome packaging. As genome assembly is a universal requirement in the Reoviridae family, this work offers an approach towards a further understanding of the sorting and packaging mechanisms of RV and related dsRNA (double-stranded RNA) viruses.
The Effect of 12 Weeks Aerobic, Resistance, and Combined Exercises on Omentin-1 Levels and Insulin Resistance among Type 2 Diabetic Middle-Aged Women

Background Recent studies have shown that omentin-1 derived from adipokines can affect physiological regulations and some metabolic dis-eases such as type 2 diabetes mellitus (T2DM). Methods The purpose of this study was to examine the impact of 12 weeks of aerobic (cycle ergometer), resistance, and combined exercises on omentin-1 level, glucose and insulin resistance indices in overweight middle age women with T2DM. In this study, 60 overweight middle age diabetic women were selected using simple random sampling and they were assigned to three groups of aerobic exercise (n=12), resistant exercise (n=12) and combined exercise (n=13), and one control group (n=15). Exercises were done in a three times per week sessions for a total of 12 weeks. Blood samples were collected before each exercise session and 24 hours after of the last session. Results Present study showed that fasting blood sugar decreased significantly in all intervention groups, while homeostasis model assessment of insulin resistance (HOMA-IR) decreased only in the aerobic and combined exercises groups. Furthermore, there was a significant increase in the omentin-1 level only in the combined exercise group. Conclusion Compared to aerobic and resistance exercises, 12 weeks of combined exercise was more efficient in improving HOMA-IR and increasing serum omentin-1 among women with T2DM.
Drosophila Ten-m and Filamin Affect Motor Neuron Growth Cone Guidance

The Drosophila Ten-m (also called Tenascin-major, or odd Oz (odz)) gene has been associated with a pair-rule phenotype. We identified and characterized new alleles of Drosophila Ten-m to establish that this gene is not responsible for segmentation defects but rather causes defects in motor neuron axon routing. In Ten-m mutants the inter-segmental nerve (ISN) often crosses segment boundaries and fasciculates with the ISN in the adjacent segment. Ten-m is expressed in the central nervous system and epidermal stripes during the stages when the growth cones of the neurons that form the ISN navigate to their targets. Over-expression of Ten-m in epidermal cells also leads to ISN misrouting. We also found that Filamin, an actin binding protein, physically interacts with the Ten-m protein. Mutations in cheerio, which encodes Filamin, cause defects in motor neuron axon routing like those of Ten-m. During embryonic development, the expression of Filamin and Ten-m partially overlap in ectodermal cells. These results suggest that Ten-m and Filamin in epidermal cells might together influence growth cone progression.
Clinical and aesthetic outcomes of immediately placed single‐tooth implants with immediate vs. delayed restoration in the anterior maxilla: A retrospective cohort study

OBJECTIVE To evaluate the impact of the timing of restoration on clinical and aesthetic outcomes following immediate implant placement in the maxillary aesthetic zone. MATERIAL AND METHODS Forty patients (16 males, 24 females) with a mean age of 50.55 ± 12.79 years (range 19-74) who had a single maxillary anterior tooth replaced by an immediate implant were included in this study. Twenty patients had their implant restored immediately with a provisional restoration (Group A), while the other 20 patients had a delayed restoration placed after 3-4 months of non-submerged healing (Group B). Clinical parameters and hard-tissue changes were evaluated after a mean follow-up period of 3 years. Aesthetic evaluation was carried out using the Pink Esthetic Score (PES) and the White Esthetic Score (WES). RESULTS No significant differences were observed in the bone level changes between the two groups: 0.05 ± 0.65 mm mesially and 0.06 ± 0.52 mm distally for the immediate group and 0.30 ± 0.54 mm mesially and 0.21 ± 0.60 mm distally for the delayed group, respectively. The median PES scores were 11.5 for Group A and 10 for Group B. Mean PES and WES scores did not differ significantly between Groups A and B: PES (11.1 vs. 10.3; p = .16) and WES (8.4 vs. 7.8; p = .16). In terms of individual PES variables, the distal papillae were significantly better in Group A as compared to Group B (p = .006). CONCLUSIONS Within the limits of this study, timing of restoration seemed to positively affect the aesthetic outcomes of immediately placed implants as evidenced by higher median PES values for the immediate restoration group when compared to the delayed restoration group. Restoration timing had no impact on the individual PES variables, except for the distal papillary height which was superior in the immediate restoration group.
sTarPicker: A Method for Efficient Prediction of Bacterial sRNA Targets Based on a Two-Step Model for Hybridization

Background Bacterial sRNAs are a class of small regulatory RNAs involved in regulation of expression of a variety of genes. Most sRNAs act in trans via base-pairing with target mRNAs, leading to repression or activation of translation or mRNA degradation. To date, more than 1,000 sRNAs have been identified. However, direct targets have been identified for only approximately 50 of these sRNAs. Computational predictions can provide candidates for target validation, thereby increasing the speed of sRNA target identification. Although several methods have been developed, target prediction for bacterial sRNAs remains challenging. Results Here, we propose a novel method for sRNA target prediction, termed sTarPicker, which was based on a two-step model for hybridization between an sRNA and an mRNA target. This method first selects stable duplexes after screening all possible duplexes between the sRNA and the potential mRNA target. Next, hybridization between the sRNA and the target is extended to span the entire binding site. Finally, quantitative predictions are produced with an ensemble classifier generated using machine-learning methods. In calculations to determine the hybridization energies of seed regions and binding regions, both thermodynamic stability and site accessibility of the sRNAs and targets were considered. Comparisons with the existing methods showed that sTarPicker performed best in both performance of target prediction and accuracy of the predicted binding sites. Conclusions sTarPicker can predict bacterial sRNA targets with higher efficiency and determine the exact locations of the interactions with a higher accuracy than competing programs. sTarPicker is available at http://ccb.bmi. ac.cn/starpicker/.
An Advertisement and Article Analysis of Skin Products and Topics in Popular Women’s Magazines: Implications for Skin Cancer Prevention

Background: In the United States, skin cancer is the most commonly diagnosed cancer, with an estimated 5 million people treated per year and annual medical treatment expenditures that exceed 8 billion dollars. The purpose of this study was two-fold: 1) to enumerate the number of advertisements for skin products with and without Sun Protection Factor (SPF) and to further analyze the specific advertisements for sunblock to determine if models, when present, depict sun safe behaviors and 2) to enumerate the number of articles related to the skin for content. Both aims include an assessment for differences in age and in magazines targeting a Black or Latina population. Methods: The sample for this cross sectional study was comprised of 99 issues of 14 popular United States magazines marketed to women, four of which market to a Black or Latina audience. Results: There were 6,142 advertisements, of which 1,215 (19.8%, 95% CI: 18.8-20.8%) were related to skin products. Among the skin product advertisements, 1,145 (93.8%, 95% CI: 93.9-96.3%) depicted skin products without SPF. The majority of skin articles (91.2%, 95% CI: 91.7-100.0%), skin product advertisements (89.9%, 95% CI: 88.2-91.6%), and sunblock advertisements featuring models (were found in magazines aimed at the older (>24 yr) audience. Conclusion: Future research on this topic could focus on the extent to which images in these magazines translate into risky health behaviors, such as sun seeking, or excessive other harmful effects of UV radiation.
Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy?

Purpose Many anticancer drugs induce apoptosis in malignant cells, and resistance to apoptosis could lead to suboptimal or no therapeutic benefit. Two cytoplasmic proteins, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2, act as a promoter and an inhibitor of apoptosis, respectively. Both Bax and Bcl-2 as well as their ratio have been regarded as prognostic markers in various cancers. However, conflicting results have been reported. A clear understanding of apoptosis has also become crucial due to reports about anti-Bcl-2 chemotherapy. We explored the relationship of Bax and Bcl-2 gene expression and their ratio with the therapeutic response in acute myeloid leukemia (AML) patients. Patients and methods Bone marrow and/or blood samples from 90 AML patients treated with cytarabine and daunorubicin were included. Expression of Bax and Bcl-2 was determined through real-time polymerase chain reaction by using ΔΔCt method of relative expression. Results Bax and Bcl-2 expression among marrow and blood samples correlated with each other (rs=0.5, p<0.01). Although bone marrow expression of Bax and Bcl-2 tended to remain higher among responders (median 1.01 and 0.29, respectively) as compared to non-responders (median 0.66 and 0.24, respectively), the difference failed to reach statistical significance (U=784.5 and 733; p=0.68 and 0.28, respectively). Conversely, Bax/Bcl-2 ratio was higher among poor responders (median 3.07 vs 1.78), though again failed to reach statistical significance (U=698.5, p=0.07). Conclusion Expression of Bax and Bcl-2 does not differ significantly among AML patients treated with cytarabine and daunorubicin in terms of remission, relapse, resistance, overall survival, and disease-free survival, thus questioning the utility of emerging anti-Bcl-2 therapy.