Miracle-dz/UniFAR-FTUs huggingface dataset:
A transient amphipathic helix in the prodomain of PCSK9 facilitates binding to low-density lipoprotein particles

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a ligand of low-density lipoprotein (LDL) receptor (LDLR) that promotes LDLR degradation in late endosomes/lysosomes. In human plasma, 30–40% of PCSK9 is bound to LDL particles; however, the physiological significance of this interaction remains unknown. LDL binding in vitro requires a disordered N-terminal region in PCSK9's prodomain. Here, we report that peptides corresponding to a predicted amphipathic α-helix in the prodomain N terminus adopt helical structure in a membrane-mimetic environment. This effect was greatly enhanced by an R46L substitution representing an atheroprotective PCSK9 loss-of-function mutation. A helix-disrupting proline substitution within the putative α-helical motif in full-length PCSK9 lowered LDL binding affinity >5-fold. Modeling studies suggested that the transient α-helix aligns multiple polar residues to interact with positively charged residues in the C-terminal domain. Gain-of-function PCSK9 mutations associated with familial hypercholesterolemia (FH) and clustered at the predicted interdomain interface (R469W, R496W, and F515L) inhibited LDL binding, which was completely abolished in the case of the R496W variant. These findings shed light on allosteric conformational changes in PCSK9 required for high-affinity binding to LDL particles. Moreover, the initial identification of FH-associated mutations that diminish PCSK9's ability to bind LDL reported here supports the notion that PCSK9-LDL association in the circulation inhibits PCSK9 activity.
The relationship between cardiometabolic risks and vitamin D levels with the degree of obesity

Aim: The aim of this study was to evaluate the cardiometabolic risk factors including vitamin D levels according to the degree of obesity in adolescents. Material and Methods: This is a retrospective cross-sectional study. A total of 363 overweight/obese adolescents aged between 11 and 18 years who were evaluated in our clinic from January 2012 to December 2015 were included in the study. The degree of obesity was calculated as the body mass index standard deviation. Hypertension, dyslipidemia, hyperinsulinemia, hyperglycemia, insulin resistance, and vitamin D deficiency were defined as cardiometabolic risk factors. Mann-Whitney U, Chi-square, Spearman and Pearson’s correlation tests, and linear regressions analyses were used for statistical analyses. Results: Of the 319 (n=319/363) adolescents, all of whose cardiometabolic risk factors were known, 267 (85.7%) had at least one cardiometabolic risk factor. The body mass index standard deviation had a positive correlation with the number of cardiometabolic risk factors (p<0.001). In the linear regression models in which sex and age were considered as covariates, an increase of one unit in the body mass index standard deviation led to an increase of 6.085 mm Hg in systolic blood pressure, 4.4 mm Hg in diastolic blood pressure, 1.59 points in HOMA-IR, 13% in insulin level, and a decrease of 2.16 ng/mL in vitamin D levels. Conclusion: In adolescents, the number of cardiometabolic risk factors increases as the degree of obesity increases. The determination of the severity of obesity can help to identify individuals at greater risk for higher blood pressure, impaired glucose metabolism, and lower serum vitamin D levels. On the other hand, the degree of obesity may not reflect the presence of abnormal lipid and glucose levels.
Spatiotemporal Analysis of Precipitation in the Sparsely Gauged Zambezi River Basin Using Remote Sensing and Google Earth Engine

Precipitation plays an important role in the food production of Southern Africa. Understanding the spatial and temporal variations of precipitation is helpful for improving agricultural management and flood and drought risk assessment. However, a comprehensive precipitation pattern analysis is challenging in sparsely gauged and underdeveloped regions. To solve this problem, Version 7 Tropical Rainfall Measuring Mission (TRMM) precipitation products and Google Earth Engine (GEE) were adopted in this study for the analysis of spatiotemporal patterns of precipitation in the Zambezi River Basin. The Kendall’s correlation and sen’s Slop reducers in GEE were used to examine precipitation trends and magnitude, respectively, at annual, seasonal and monthly scales from 1998 to 2017. The results reveal that 10% of the Zambezi River basin showed a significant decreasing trend of annual precipitation, while only 1% showed a significant increasing trend. The rainy-season precipitation appeared to have a dominant impact on the annual precipitation pattern. The rainy-season precipitation was found to have larger spatial, temporal and magnitude variation than the dry-season precipitation. In terms of monthly precipitation, June to September during the dry season were dominated by a significant decreasing trend. However, areas presenting a significant decreasing trend were rare (<12% of study area) and scattered during the rainy-season months (November to April of the subsequent year). Spatially, the highest and lowest rainfall regions were shifted by year, with extreme precipitation events (highest and lowest rainfall) occurring preferentially over the northwest side rather than the northeast area of the Zambezi River Basin. A “dry gets dryer, wet gets wetter” (DGDWGW) pattern was also observed over the study area, and a suggestion on agriculture management according to precipitation patterns is provided in this study for the region. This is the first study to use long-term remote sensing data and GEE for precipitation analysis at various temporal scales in the Zambezi River Basin. The methodology proposed in this study is helpful for the spatiotemporal analysis of precipitation in developing countries with scarce gauge stations, limited analytic skills and insufficient computation resources. The approaches of this study can also be operationally applied to the analysis of other climate variables, such as temperature and solar radiation.
Knowledge and Attitude Toward Strabismus in Western Province, Saudi Arabia

Background Strabismus is a common eye condition having a potential subsequent impact on the psychological and socioeconomic domains of individuals suffering from strabismus. Therefore, this study aimed to find out the level of knowledge and treatability of strabismus in the western province of Saudi Arabia. Methods An observational cross-sectional study was conducted in 2018 among people who live in the western region of Saudi Arabia and were age 16 and above by using an online self-administered questionnaire. Results Out of 589 participants, 52.8% reported the correct definition of strabismus. The majority of responders agreed that strabismus is treatable (71.5%). In addition, a statically significant relation was found between knowledge of strabismus treatability and age, gender, work state, and level of education. Most participants were aware of the risk factors and complications of strabismus. Conclusion Our study found that the majority of participants had good knowledge of the definition, treatment, and complications of untreated strabismus. Participant’s age, education level, work state, and income were the main factors found to be significantly associated with knowledge of strabismus treatment options.
Faecal analyses and alimentary tracers reveal the foraging ecology of two sympatric bats

We used three complementary methods to assess the diet of two insectivorous bat species: one an obligate aerial hunter, Miniopterus natalensis, and the other Myotis tricolor whose morphology and taxonomic affiliation to other trawling bats suggests it may be a trawler (capturing insects from the water surface with its feet and tail). We used visual inspection, stable isotope values and fatty acid profiles of insect fragments in bat faeces sampled across five sites to determine the contribution of aquatic and terrestrial arthropods to the diets of the two species. The niche widths of M. tricolor were generally wider than those of Miniopterus natalensis but with much overlap, both taking aquatic and terrestrial insects, albeit in different proportions. The diet of M. tricolor had high proportions of fatty acids (20:5ω3 and 22:6ω3) that are only obtainable from aquatic insects. Furthermore, the diet of M. tricolor had higher proportions of water striders (Gerridae) and whirligig beetles (Gyrinidae), insects obtainable via trawling, than Miniopterus natalensis. These results suggest both species are flexible in their consumption of prey but that M. tricolor may use both aerial hawking and trawling, or at least gleaning, to take insects from water surfaces. The resultant spatial segregation may sufficiently differentiate the niches of the two species, allowing them to co-exist. Furthermore, our results emphasize that using a combination of methods to analyse diets of cryptic animals yields greater insights into animal foraging ecology than any of them on their own.
Romo1 is involved in the immune response of glioblastoma by regulating the function of macrophages

Reactive oxygen species (ROS) modulator 1 (Romo1) is a mitochondrial membrane protein that is essential for the regulation of mitochondrial ROS production and redox sensing. Although the physiological functions of Romo1 have been studied for the past few years, the role of Romo1 in cancer remained unclear. In this study, we found that the high expression of Romo1 is associated with the poor prognosis of glioblastoma patients. Further study revealed that Romo1 is highly expressed in macrophages, indicating that the overexpression of Romo1 may participate in the function of macrophages and contribute to the progression of glioblastoma. Through the glioblastoma mouse model, we found that the overexpression of Romo1 in bone marrow cells significantly inhibited the immune response within tumor microenvironment, and that the overexpression of Romo1 resulted in the M2 polarization of bone marrow derived macrophages (BMDMs) through mTORC1 signaling pathway. In addition, the inhibition of Romo1 combining with anti-PD-1 immunotherapy significantly improved the survival outcome of glioblastoma in mouse model. Collectively, our study highlights the important role of Romo1 in immune response especially the function of macrophages, and implicates it as a potential target of immunotherapy for glioblastoma.
Oxidative Stress-Induced DNA Damage and Apoptosis in Clove Buds-Treated MCF-7 Cells

In recent decades, several spices have been studied for their potential in the prevention and treatment of cancer. It is documented that spices have antioxidant, anti-inflammatory, immunomodulatory, and anticancer effects. The main mechanisms of spices action included apoptosis induction, proliferation, migration and invasion of tumour inhibition, and sensitization of tumours to radiotherapy and chemotherapy. In this study, the ability of clove buds extract (CBE) to induce oxidative stress, DNA damage, and stress/survival/apoptotic pathways modulation were analysed in MCF-7 cells. We demonstrated that CBE treatment induced intrinsic caspase-dependent cell death associated with increased oxidative stress mediated by oxygen and nitrogen radicals. We showed also the CBE-mediated release of mitochondrial pro-apoptotic factors, signalling of oxidative stress-mediated DNA damage with modulation of cell antioxidant SOD (superoxide dismutase) system, and modulation activity of the Akt, p38 MAPK, JNK and Erk 1/2 pathways.
Awareness of Female Genital Mutilation/Cutting Among the General Population in 2019: A Survey-based Study in Saudi Arabia

Background Female genital mutilation/cutting (FGM/C) includes “all procedures that include the removal of the external female genitalia, partially or totally, using a blade or shard of glass for non-medical reasons. ” FGM/C is a harmful procedure known to violates a person's human rights. This study aims to assess the level of knowledge regarding FGM/C in Saudi Arabia. Methodology A survey-based cross-sectional study was conducted in 2019 among a representative sample of the general population of Saudi Arabia. The questionnaire consisted of a set of questions dealing with the knowledge of FGM/C. We analyzed the data by using the Statistical Package for Social Sciences (SPSS) version 21 IBM Corp., Armonk, NY), and the results were acquired by applying Pearson’s chi-square test and calculating the frequencies. Results The study included 659 participants; 80.4% were females and 19.6% were males. About 93.8% knew about FGM/C while 68.3% were aware of the health consequences of female circumcision. The most common sources of information were the Internet and social media (54.4%). The overall prevalence of circumcision among the female participants was 9.4%. Conclusion Generally, our population had good knowledge of FGM/C. However, it is not enough to eliminate this practice. Health and human rights education campaigns and programs should be done to enhance public awareness. In addition, more researches about the prevalence of this tradition should be taken into consideration.
Update: Product, Substance-Use, and Demographic Characteristics of Hospitalized Patients in a Nationwide Outbreak of E-cigarette, or Vaping, Product Use–Associated Lung Injury — United States, August 2019–January 2020

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders continue to investigate a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). EVALI patients in Illinois, Utah, and Wisconsin acquired tetrahydrocannabinol (THC)-containing products primarily from informal sources (2,3). This report updates demographic characteristics and self-reported sources of THC- and nicotine-containing e-cigarette, or vaping, products derived from EVALI patient data reported to CDC by state health departments. As of January 7, 2020, among 1,979 (76%) patients with available data on substance use, a total of 1,620 (82%) reported using any THC-containing products, including 665 (34%) who reported exclusive THC-containing product use. Use of any nicotine-containing products was reported by 1,128 (57%) patients, including 264 (13%) who reported exclusive nicotine-containing product use. Among 809 (50%) patients reporting data on the source of THC-containing products, 131 (16%) reported acquiring their products from only commercial sources (i.e., recreational dispensaries, medical dispensaries, or both; vape or smoke shops; stores; and pop-up shops), 627 (78%) from only informal sources (i.e., friends, family, in-person or online dealers, or other sources), and 51 (6%) from both types of sources. Among 613 (54%) EVALI patients reporting nicotine-containing product use with available data on product source, 421 (69%) reported acquiring their products from only commercial sources, 103 (17%) from only informal sources, and 89 (15%) from both types of sources. Adolescents aged 13-17 years were more likely to acquire both THC- and nicotine-containing products from informal sources than were persons in older age groups. The high prevalence of acquisition of THC-containing products from informal sources by EVALI patients reinforces CDC's recommendation to not use e-cigarette, or vaping, products that contain THC, especially those acquired from informal sources. Although acquisition of nicotine-containing products through informal sources was not common overall, it was common among persons aged <18 years. While the investigation continues, CDC recommends that the best way for persons to ensure that they are not at risk is to consider refraining from the use of all e-cigarette, or vaping, products.
Identification of putative Type-I sex pheromone biosynthesis-related genes expressed in the female pheromone gland of Streltzoviella insularis

Species-specific sex pheromones play key roles in moth sexual communication. Although the general pathway of Type-I sex pheromone biosynthesis is well established, only a handful of genes encoding enzymes involved in this pathway have been characterized. Streltzoviella insularis is a destructive wood-boring pest of many street trees in China, and the female sex pheromone of this species comprises a blend of (Z)-3-tetradecenyl acetate, (E)-3-tetradecenyl acetate, and (Z)-5-dodecenyl acetate. This organism therefore provides an excellent model for research on the diversity of genes and molecular mechanisms involved in pheromone production. Herein, we assembled the pheromone gland transcriptome of S. insularis by next-generation sequencing and identified 74 genes encoding candidate key enzymes involved in the fatty acid biosynthesis, β-oxidation, and functional group modification. In addition, tissue expression patterns further showed that an acetyl-CoA carboxylase and two desaturases were highly expressed in the pheromone glands compared with the other tissues, indicating possible roles in S. insularis sex pheromone biosynthesis. Finally, we proposed putative S. insularis biosynthetic pathways for sex pheromone components and highlighted candidate genes. Our findings lay a solid foundation for understanding the molecular mechanisms underpinning S. insularis sex pheromone biosynthesis, and provide potential targets for disrupting chemical communication that could assist the development of novel pest control methods.
Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of Escherichia coli O157:H7 during Host-Bacterial Interactions in vitro

Enterohemorrhagic Escherichia coli (EHEC) strains are food-borne pathogens that can cause different clinical conditions. Shiga toxin 2a and/or 2c (Stx2)-producing E. coli O157:H7 is the serotype most frequently associated with severe human disease. In this work we analyzed the hypothesis that host cells participate in Stx2 production, cell damage, and inflammation during EHEC infection. With this aim, macrophage-differentiated THP-1 cells and the intestinal epithelial cell line HCT-8 were incubated with E. coli O157:H7. A time course analysis of cellular and bacterial survival, Stx2 production, stx2 transcription, and cytokine secretion were analyzed in both human cell lines. We demonstrated that macrophages are able to internalize and kill EHEC. Simultaneously, Stx2 produced by internalized bacteria played a major role in macrophage death. In contrast, HCT-8 cells were completely resistant to EHEC infection. Besides, macrophages and HCT-8 infected cells produce IL-1β and IL-8 inflammatory cytokines, respectively. At the same time, bacterial stx2-specific transcripts were detected only in macrophages after EHEC infection. The interplay between bacteria and host cells led to Stx production, triggering of inflammatory response and cell damage, all of which could contribute to a severe outcome after EHEC infections.
Spatial and Temporal Variations of Particulate Organic Carbon Sinking Flux in Global Ocean from 2003 to 2018

The monitoring of particulate organic carbon (POC) flux at the bottom of the euphotic layer in global ocean using remote sensing satellite data plays an important role in clarifying and evaluating the ocean carbon cycle. Based on the in situ POC flux data, this paper evaluated various estimation models. The global ocean POC flux from 2003 to 2018 was calculated using the optimal model, and its temporal and spatial variation characteristics were analyzed. In general, the annual average of global ocean POC flux is about 8.5–14.3 Gt C yr − 1 for period of 2003–2018. In the spatial dimension, the POC flux in the mid-latitude ocean (30–60°) is higher than that in the low-latitude (0–30°). The POC flux in Continental Margins with water depth less than 2000 m accounted for 30% of global ocean, which should receive more attention in global carbon cycle research. In the time dimension, the global POC flux decreases year by year generally, but the POC flux abnormally decreases during El Niño and increases during La Niña. In addition, due to global warming, sea ice melting, and bipolar sea area expansion, POC flux in high-latitude oceans (60–90°) is increasing year by year.
Effect of Thermocycling, Surface Treatments and Microstructure on the Optical Properties and Roughness of CAD-CAM and Heat-Pressed Glass Ceramics

Dental ceramic restorations are widely spread nowadays due to their aesthetics and biocompatibility. In time, the colour and structure of these ceramic materials can be altered by aging processes. How does artificial aging affect the optical and surface roughness of ceramics? This study aims to assess the effect of thermocycling, surface treatments and microstructure upon translucency, opalescence and surface roughness on CAD-CAM and heat-pressed glass-ceramic. Forty-eight samples (1.5 mm thickness) were fabricated from six types of A2 MT ceramic: heat-pressed and milled glass-ceramic (feldspathic, lithium disilicate and zirconia reinforced lithium silicate). The samples were obtained respecting the manufacturer’s instructions. The resulted surfaces (n = 96) were half glazed and half polished. The samples were subjected to thermocycling (10,000 cycles) and roughness values (Ra and Rz), colour coordinates (L*, a*, b*) and microstructural analyses were assessed before and after thermocycling. Translucency (TP) and opalescence (OP) were calculated. Values were statistically analysed using ANOVA test (one way). TP and OP values were significantly different between heat-pressed and milled ceramics before and also after thermocycling (p < 0.001). Surface treatments (glazing and polishing) had a significant effect on TP and OP and surface roughness (p < 0.05). The heat-pressed and milled zirconia reinforced lithium silicate glass-ceramic experienced a loss in TP and OP. Ra and Rz increased for the glazed samples, TP and OP decreased for all the samples after thermocycling. Microstructural analyse revealed that glazed surfaces were more affected by the thermocycling and especially for the zirconia reinforced lithium silicate ceramic. Optical properties and surface roughness of the chosen ceramic materials were affected by thermocycling, surface treatments and microstructural differences. The least affected of the ceramics was the lithium disilicate ceramic heat-pressed polished and glazed.
Children's Response Bias and Identification of Misarticulated Words

Purpose The purpose of this study was to examine whether children's identification of misarticulated words as real objects was influenced by an inherent bias toward selecting real objects or whether a change in experimental conditions could impact children's selections. Method Forty preschool children aged 4 years 0 months to 6 years 11 months across 2 experiments heard accurate productions of real words (e.g., “leaf”), misarticulated words (e.g., “weaf” and “yeaf”), and unrelated nonwords (e.g., “geem”). Within the misarticulated words, the commonness of the substitute was controlled to be “common” or “uncommon. ” Using the MouseTracker software, children were asked to select between a real object (e.g., a leaf) and a novel object (Experiment 1) or between a real object (e.g., a leaf) and a blank square, which represented a hidden object (Experiment 2). Results Consistent with previous findings, children chose real objects significantly more when they heard accurate productions (e.g., “leaf”) than misarticulated productions (e.g., “weaf” or “yeaf”) across both experiments. In misarticulation conditions, real object selections were lower than in the previous study; however, children chose real objects significantly more in the common misarticulation condition than in the uncommon misarticulation condition. Conclusions The results of this study are consistent with previous findings. Children's behavioral responses depended upon the task. Despite these differences in the task, children demonstrated ease in integrating variability into their word identification.