Miracle-dz/UniFAR-FTUs huggingface dataset:
Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza

The D222G/N substitution in the hemagglutinin (HA) protein of influenza A(H1N1)pdm09 virus has been reported to be associated with disease severity and mortality in numerous previous studies. In the present study, 75% of lower respiratory samples contained heterogeneous influenza populations that carried different amino acids at position 222 of the HA protein, whereas all upper respiratory samples only contained the wild-type 222D. ABSTRACT The influenza A(H1N1)pdm09 virus emerged in April 2009 with an unusual incidence of severe disease and mortality, and currently circulates as a seasonal influenza virus. Previous studies using consensus viral genome sequencing data have overlooked the viral genomic and phenotypic diversity. Next-generation sequencing (NGS) may instead be used to characterize viral populations in an unbiased manner and to measure within-host genetic diversity. In this study, we used NGS analysis to investigate the within-host genetic diversity of influenza A(H1N1)pdm09 virus in the upper and lower respiratory samples from nine patients who were admitted to the intensive care unit (ICU). A total of 47 amino acid substitution positions were found to differ between the upper and lower respiratory tract samples from all patients. However, the D222G/N substitution in hemagglutinin (HA) protein was the only amino acid substitution common to multiple patients. Furthermore, the substitution was detected only in the six samples from the lower respiratory tract. Therefore, it is important to investigate influenza A(H1N1)pdm09 virus populations using multiple paired samples from the upper and lower respiratory tract to avoid overlooking potentially important substitutions, especially in patients with severe disease. IMPORTANCE The D222G/N substitution in the hemagglutinin (HA) protein of influenza A(H1N1)pdm09 virus has been reported to be associated with disease severity and mortality in numerous previous studies. In the present study, 75% of lower respiratory samples contained heterogeneous influenza populations that carried different amino acids at position 222 of the HA protein, whereas all upper respiratory samples only contained the wild-type 222D. These results suggest the influenza A(H1N1)pdm09 virus has diversified inside the host owing to differences in tissue specificity. In this study, the within-host genetic diversity of influenza A(H1N1)pdm09 virus was investigated for the first time using next-generation sequencing analysis of the viral whole-genome in samples extracted from the upper and lower respiratory tracts of patients with severe disease.
Inducible Guanylate-Binding Protein 7 Facilitates Influenza A Virus Replication by Suppressing Innate Immunity via NF-κB and JAK-STAT Signaling Pathways

So far, few studies have mentioned the distinct function of guanylate-binding protein 7 (GBP7) on virus infection. Here, we reported that GBP7 expression was significantly upregulated in the lungs of mice, human PBMCs, and A549 cells during IAV infection. ABSTRACT Guanylate-binding protein 7 (GBP7) belongs to the GBP family, which plays key roles in mediating innate immune responses to intracellular pathogens. Thus far, GBP7 has been reported to be a critical cellular factor against bacterial infection. However, the relationship between GBP7 and influenza A virus (IAV) replication is unknown. Here, we showed that GBP7 expression was significantly upregulated in the lungs of mice, human peripheral blood mononuclear cells (PBMCs), and A549 cells during IAV infection. Using the CRISPR-Cas9 system and overexpression approaches, it was found that GBP7 knockout inhibited IAV replication by enhancing the expression of IAV-induced type I interferon (IFN), type III IFN, and proinflammatory cytokines. Conversely, overexpression of GBP7 facilitated IAV replication by suppressing the expression of those factors. Furthermore, GBP7 knockout enhanced IAV-induced nuclear factor-κB (NF-κB) activation and phosphorylation of stat1 and stat2; overexpression of GBP7 had the opposite effect. Our data indicated that GBP7 suppresses innate immune responses to IAV infection via NF-κB and JAK-STAT signaling pathways. Taken together, upon IAV infection, the induced GBP7 facilitated IAV replication by suppressing innate immune responses to IAV infection, which suggested that GBP7 serves as a therapeutic target for controlling IAV infection. IMPORTANCE So far, few studies have mentioned the distinct function of guanylate-binding protein 7 (GBP7) on virus infection. Here, we reported that GBP7 expression was significantly upregulated in the lungs of mice, human PBMCs, and A549 cells during IAV infection. GBP7 facilitated IAV replication by suppressing the expression of type I interferon (IFN), type III IFN, and proinflammatory cytokines. Furthermore, it was indicated that GBP7 suppresses innate immune responses to IAV infection via NF-κB and JAK-STAT signaling pathways. Taken together, our results elucidate a critical role of GBP7 in the host immune system during IAV infection.
Ceramide contributes to pathogenesis and may be targeted for therapy in VCP inclusion body myopathy.

BACKGROUND/OBJECTIVE Knock-in homozygote VCPR155H/R155H mutant mice are a lethal model of Valosin Containing Protein (VCP)-associated Inclusion Body Myopathy, Paget disease of bone, frontotemporal dementia, and amyotropic lateral sclerosis. Ceramide (d18:1/16:0) levels are elevated in skeletal muscle of the mutant mice, compared to wild-type controls. Moreover, exposure to a lipid-enriched diet reverses lethality, improves myopathy and normalizes ceramide levels in these mutant mice, suggesting that dysfunctions in lipid-derived signaling are critical to disease pathogenesis. Here, we investigated the potential role of ceramide in VCP disease using pharmacological agents that manipulate the ceramide levels in myoblast cultures from VCP mutant mice and VCP patients. METHODS Myoblasts from wild-type, VCPR155H/+ and VCPR155H/R155H mice, as well as patient induced pluripotent stem cells (iPSCs), were treated with an inhibitor of ceramide degradation to increase ceramide via acid ceramidase (ARN082) for proof of principle. Three chemically distinct inhibitors of ceramide biosynthesis via serine palmitoyl-CoA transferase (L-cycloserine, myriocin or ARN14494) used as a therapeutic strategy to reduce ceramide in myoblasts. RESULTS Acid ceramidase inhibitor, ARN082, elevated cellular ceramide levels and concomitantly enhanced pathology. Conversely inhibitors of ceramide biosynthesis L-cycloserine, myriocin and ARN14494 reduced ceramide production. The results point to ceramide-mediated signaling as a key contributor to pathogenesis in VCP disease, and suggests that manipulating this pathway by blocking ceramide biosynthesis might exert beneficial effects in patients with this condition. CONCLUSION The ceramide pathway appears to be critical in VCP pathogenesis, and small-molecule inhibitors of ceramide biosynthesis might provide therapeutic benefit in VCP and, related neurodegenerative diseases.
Ice elevation change from Swath Processing of CryoSat SARIn Mode Data

Reference and repeat-observations of Glacier and Ice Sheet Margin (GISM) topography are critical to identify changes in ice elevation, provide estimates of mass gain or loss and thus quantify the contribution of the cryosphere to sea level rise (e.g. McMillan et al., 2014). The Synthetic Interferometric Radar Altimeter (SIRAL) onboard the ESA radar altimetry CryoSat (CS) mission has collected ice elevation measurements since 2010. The corresponding SARIn mode of operation, activated over GISM areas, provides high spatial resolution in the along-track direction while resolving the angular origin of echoes (i.e. across-track). The current ESA SARIn processor calculates the elevation of the Point Of Closest Approach (POCA) within each waveform and maps of elevation change in Antarctica and Greenland have been produced using the regular CS height product (McMillan et al., 2014; Helm et al., 2014). Data from the CS-SARIn mode has also been used to produce measurements of ice elevation beyond the POCA, also known as swath elevation (Hawley et al. 2009; Gray et al., 2013; ESA-STSE CryoTop project). Here we use the swath processing approach to generate maps of ice elevation change from selected regions around the margins of the Greenland and Antarctic Ice Sheets. We discuss the impact of the swath processing on the spatial resolution and precision of the resulting ice elevation field and compare our results to current dh/dt estimates.
Prospective Analysis of Leisure-Time Physical Activity in Midlife and Beyond and Brain Damage on MRI in Older Adults

Objective To test the hypothesis that greater levels of leisure-time moderate to vigorous intensity physical activity (MVPA) in midlife or late life are associated with larger gray matter volumes, less white matter disease, and fewer cerebrovascular lesions measured in late life, we utilized data from 1,604 participants enrolled in the Atherosclerosis Risk in Communities study. Methods Leisure-time MVPA was quantified using a past-year recall, interviewer-administered questionnaire at baseline and 25 years later and classified as none, low, middle, and high at each time point. The presence of cerebrovascular lesions, white matter hyperintensities (WMH), white matter integrity (mean fractional anisotropy [FA] and mean diffusivity [MD]), and gray matter volumes were quantified with 3T MRI in late life. The odds of cerebrovascular lesions were estimated with logistic regression. Linear regression estimated the mean differences in WMH, mean FA and MD, and gray matter volumes. Results Among 1,604 participants (mean age 53 years, 61% female, 27% Black), 550 (34%), 176 (11%), 250 (16%), and 628 (39%) reported no, low, middle, and high MVPA in midlife, respectively. Compared to no MVPA in midlife, high MVPA was associated with more intact white matter integrity in late life (mean FA difference 0.13 per SD [95% confidence interval (CI) 0.004, 0.26]; mean MD difference −0.11 per SD [95% CI −0.21, −0.004]). High MVPA in midlife was also associated with a lower odds of lacunar infarcts (odds ratio 0.68, 95% CI 0.46, 0.99). High MVPA was not associated with gray matter volumes. High MVPA compared to no MVPA in late life was associated with most brain measures. Conclusion Greater levels of physical activity in midlife may protect against cerebrovascular sequelae in late life.
1H NMR Characterization of HPAm/Cr(III) Acetate Polymer Gel Components

Abstract Low-field 1 H nuclear magnetic resonance (NMR) was used to characterize the components of polymer gels formulated with partly hydrolyzed polyacrylamide (HPAm) and Cr(III) acetate. Changes in the NMR relaxation times were used to characterize samples of polymer, cross-linker, polymer solutions, and cross-linker solutions in bulk and in porous media. The results obtained indicated that changes of HPAm concentration do not have a significant effect on the relaxation times, while changes in Cr(III) acetate concentration do. Therefore, the concentration of cross-linker is the most critical variable in the process of characterizing HPAm/Cr(III) acetate polymer gels using low-field 1 H NMR.
Contribution to the investigation of the ternary Lu -Cu-Sn system

determined using X-ray powder diffraction. The Lu 1.8 Cu 9.2 Sn 2.8 compound crystallizes in the Dy 1.9 Cu 9.2 Sn 2.8 structure type (space group P63/mmc ), whereas the Lu 3Cu 4Sn 4 stannide belongs to the Tm 3Cu 4Sn 4 structure type (space group C2/ m). The formation of a substitutional solid solution LuCu 5-xSn x up to 15 at. % Sn was observed.
APR-246 induces early cell death by ferroptosis in acute myeloid leukemia

APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia (AML). APR-246 reactivates the transcriptional activity of p53 mutants by facilitating their binding to DNA target sites. Recent studies in solid cancers have found that APR-246 can also induce p53-independent cell death. In this study, we demonstrate that AML cell death occurring early after APR-246 exposure is suppressed by iron chelators, lipophilic antioxidants and inhibitors of lipid peroxidation, and correlates with the accumulation of markers of lipid peroxidation, thus fulfilling the definition of ferroptosis, a recently described cell death process. The capacity of AML cells to detoxify lipid peroxides by increasing their cystine uptake to maintain major antioxidant molecule glutathione biosynthesis after exposure to APR-246 may be a key determinant of sensitivity to this compound. The association of APR-246 with induction of ferroptosis (either by pharmacological compounds, or genetic inactivation of SLC7A11 or GPX4) had a synergistic effect on the promotion of cell death, both in vivo and ex vivo.
Polyamines Influence Mouse Sperm Channels Activity

Polyamines are ubiquitous polycationic compounds that are highly charged at physiological pH. While passing through the epididymis, sperm lose their capacity to synthesize the polyamines and, upon ejaculation, again come into contact with the polyamines contained in the seminal fluid, unleashing physiological events that improve sperm motility and capacitation. In the present work, we hypothesize about the influence of polyamines, namely, spermine, spermidine, and putrescine, on the activity of sperm channels, evaluating the intracellular concentrations of chloride [Cl−]i, calcium [Ca2+]i, sodium [Na+]i, potassium [K+]i, the membrane Vm, and pHi. The aim of this is to identify the possible regulatory mechanisms mediated by the polyamines on sperm-specific channels under capacitation and non-capacitation conditions. The results showed that the presence of polyamines did not directly influence the activity of calcium and chloride channels. However, the results suggested an interaction of polyamines with sodium and potassium channels, which may contribute to the membrane Vm during capacitation. In addition, alkalization of the pHi revealed the possible activation of sperm-specific Na+/H+ exchangers (NHEs) by the increased levels of cyclic AMP (cAMP), which were produced by soluble adenylate cyclase (sAC) and interact with the polyamines, evidence that is supported by in silico analysis.
Effect of Processing and Storage on The Antioxidant Activity of Frozen and Pasteurized Shadblow Serviceberry (Amelanchier canadensis)

Serviceberry fruits were pasteurised in glass jars at two temperatures, 85 and 100°C, while another batch was packed in polyethylene bags and frozen at a temperature of −20 ± °C. Processed fruits were stored for 10 months: frozen fruit at −20 ± 1°C; and pasteurised fruit at room temperature without access to light. Refrigerated storage and pasteurization lowered the DPPH antioxidant activity of serviceberry fruit. In the former, the change was not great, whilst pasteurisation caused an approximately twofold increase in EC50. On the basis of total anthocyanin content and total polyphenolic content measurements, it would appear that the antioxidant properties of serviceberry were affected mainly by anthocyanins. Pasteurising at 100°C allowed slightly better preservation of these compounds during long-term storage.
BITTERNESS REDUCTION AND ENZYMATIC TRANSFORMATION OF GINSENOSIDES FROM KOREAN RED GINSENG (PANAX GINSENG) EXTRACT

In the paper, we studied the bitterness reduction and the changes in ginsenoside contents of ginseng extract by using commercial amylases and viscozyme, PC-0 (non-enzymatic treatment), PC-1 (spezyme prime treatment) and PC-2 (spezyme prime, optidex and viscozyme treatment). The PC-2 treatment resulted in high levels of total sugar (236.21 mg/mL), uronic acid (9,039.40 µg/mL), polyphenols (608.57 µg/mL) and solid contents (15.66%). Total ginsenosides contents following PC-2, PC-1 and PC-0 treatments of red ginseng were 31,850.6, 21,075.7 and 15,958.1 µg/mL, respectively. The ginsenoside Rh2 was only found after PC-2 treatment of red ginseng. The Rb2 and Rc contents following PC-2-treatment of red ginseng were 999.91 and 2,543.76 µg/mL, respectively. The contents of the ginsenosides Rb1 and Road decreased from 5,699.38 and 1,889.72 µg/mL (in PC-0) to 3,176.43 and 1,597.12 µg/mL (in PC-2), respectively, and that of Rg3 increased from 511.0 µg/mL (in PC-0) to 2,346.5 µg/mL (in PC-2). The bitterness value of PC-2-treated red ginseng decreased from 5.80 (PC-0) to 3.40 (PC-2). Optidex and viscozyme treatment increased total sugar, uronic acid, polyphenol and solid contents and reduced the bitterness of red ginseng extract. In particular, Rb2 and Rc were transformed into Rg3 or Rh2 and Rb1 was transformed into Rg3 following the optidex and viscozyme treatment. PRACTICAL APPLICATION Korean ginseng is recognized worldwide as a natural healthy food along with the global trend of preference for natural products. Ginsenosides are abundant in ginseng, especially ginsenoside metabolites, such as ginsenoside Rg3, Rg5, Rk1, CK, Rh1 and Rg2; the metabolites are attracting more attentions for their biological properties and health benefits. However, ginseng has an unfamiliar, bitter/sweet/earthy flavor, quite unlike most foods consumed in the west. We have also used enzymes (spezyme, optidex and viscozyme) for ginseng extraction and to reduce the bitterness and to change ginsenosides glycosides to ginsenosides metabolites.
ToF‐SIMS characterization of the lipid layer on the hair surface. I: the damage caused by chemical treatments and UV radiation

In this study, we investigated how the lipids bound to the outermost surface of human hair are affected by chemical treatments such as hair bleach and ultraviolet (UV) radiation using time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). Many lipid components are bound covalently via a thioester or ester linkage on the outermost surface of hair. We studied how these components are changed by chemical treatment. It was found that the fatty acids covalently bound via a thioester linkage are removed more easily than those with an ester linkage. Eighty percent of the 18‐MEA (18‐methyleicosanoic acid), which is a major component of lipids, was removed in a single bleach treatment, and most had vanished entirely after three treatments. We also investigated the influence of UV radiation and found that the amount of 18‐MEA decreased with the radiation time. More than 90% of the 18‐MEA was removed by UV radiation with corresponding exposure of three summer months. Copyright © 2010 John Wiley & Sons, Ltd.
ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels

Pannexin 1 (Panx1) is a membrane channel implicated in numerous physiological and pathophysiological processes via its ability to support release of ATP and other cellular metabolites for local intercellular signaling. However, to date, there has been no direct demonstration of large molecule permeation via the Panx1 channel itself, and thus the permselectivity of Panx1 for different molecules remains unknown. To address this, we expressed, purified, and reconstituted Panx1 into proteoliposomes and demonstrated that channel activation by caspase cleavage yields a dye-permeable pore that favors flux of anionic, large-molecule permeants (up to ~1 kDa). Large cationic molecules can also permeate the channel, albeit at a much lower rate. We further show that Panx1 channels provide a molecular pathway for flux of ATP and other anionic (glutamate) and cationic signaling metabolites (spermidine). These results verify large molecule permeation directly through caspase-activated Panx1 channels that can support their many physiological roles.
Atomic force microscopy imaging and cutting of beaded carbon nanotubes deposited on glass

We use contact force mode atomic force microscopy (AFM) to study the structures and to cut carbon nanotubes (CNTs) adsorbed on a glass slide. In addition to regular CNTs, beaded carbon nanotubes (BCNTs) were also observed when preparing products using electric current heating with the pencil technique. Imaging by contact force mode AFM could be achieved at low contact force, whereas cutting could be operated at a higher contact force in conjunction with the y‐scan direction being disabled. Cutting of BCNTs can be done without any translation of the beaded tubes. It is believed that the similar ingredients of the beaded oxides and the glass slide make them bond preferentially by chemical force. Furthermore, the morphologies were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Copyright © 2002 John Wiley & Sons, Ltd.
Emotion as a source of moral understanding in conservation

Recent debates around the meaning and implications of compassionate conservation suggest that some conservationists consider emotion a false and misleading basis for moral judgment and decision making. We trace these beliefs to a long‐standing, gendered sociocultural convention and argue that the disparagement of emotion as a source of moral understanding is both empirically and morally problematic. According to the current scientific and philosophical understanding, reason and emotion are better understood as partners, rather than opposites. Nonetheless, the two have historically been seen as separate, with reason elevated in association with masculinity and emotion (especially nurturing emotion) dismissed or delegitimated in association with femininity. These associations can be situated in a broader, dualistic, and hierarchical logic used to maintain power for a dominant male (White, able‐bodied, upper class, heterosexual) human class. We argue that emotion should be affirmed by conservationists for the novel and essential insights it contributes to conservation ethics. We consider the specific example of compassion and characterize it as an emotional experience of interdependence and shared vulnerability. This experience highlights conservationists’ responsibilities to individual beings, enhancing established and widely accepted beliefs that conservationists have a duty to protect populations, species, and ecosystems (or biodiversity). We argue compassion, thus understood, should be embraced as a core virtue of conservation.
A New Estimation Method for the Biological Interaction Predicting Problems

For the past decades, computational methods have been developed to predict various interactions in biological problems. Usually these methods treated the predicting problems as semi-supervised problem or positive-unlabeled(PU) learning problem. Researchers focused on the prediction of unlabeled samples and hoped to find novel interactions in the datasets they collected. However, most of the computational methods could only predict a small proportion of undiscovered interactions and the total number was unknown. In this paper, we developed an estimation method with deep learning to calculate the number of undiscovered interactions in the unlabeled samples, derived its asymptotic interval estimation, and applied it to the compound synergism dataset, drug-target interaction(DTI) dataset and MicroRNA-disease interaction dataset successfully. Moreover, this method could reveal which dataset contained more undiscovered interactions and would be a guidance for the experimental validation. Furthermore, we compared our method with some mixture proportion estimators and demonstarted the efficacy of our method. Finally, we proved that AUC and AUPR were related with the number of undiscovered interactions, which was regarded as another evaluation indicator for the computational methods.