Miracle-dz/UniFAR-FTUs huggingface dataset:
A role for Rab5 in structuring the endoplasmic reticulum

The ER is a single contiguous compartment (Terasaki and Jaffe, 1991; Cole et al., 1996; Terasaki, 2000) that is differentiated into at least three functionally distinct domains: rough ER, smooth ER, and nuclear envelope (Palade, 1955; Watson, 1955; Baumann and Walz, 2001). Cumulatively, these ER domains partition the nuclear contents from the cytoplasm and direct the synthesis of lipids, as well as membrane and secretory proteins (Estrada de Martin et al., 2005; Hetzer et al., 2005; Margalit et al., 2005; Shibata et al., 2006; Vedrenne and Hauri, 2006). The ER is also a signaling organelle that serves as a storage site for intracellular calcium and regulates its uptake and release into the cytoplasm (Papp et al., 2003). Structurally, the ER network consists of membrane tubules, fl attened sheets, and cisternae. The thickness of ER sheets is similar to the diameter of ER tubules, typically 60–100 nm, suggesting that common structural elements underlie these morphologically distinct forms (Shibata et al., 2006). The differing morphologies exhibited by ER domains likely contribute to their distinct functions. Rough ER, specialized for protein synthesis and folding, is often found in ribosome-studded sheets. In contrast, smooth ER, a site for lipid synthesis, contact with other organelles, and vesicle budding and fusion, lacks ribosomes and is often tubular (Baumann and Walz, 2001). The nuclear envelope, perhaps the most highly differentiated region of the ER, is a polarized sheet that regulates the movement of macromolecules between the nuclear space and the cytoplasm (Hetzer et al., 2005; Prunuske and Ullman, 2006). The membrane on one side of the sheet, the outer nuclear membrane (ONM), faces the cytoplasm, and on the opposite side of the lumen, the inner nuclear membrane (INM) faces the chromatin. Nuclear pores, gated channels between the cytoplasm and the nuclear interior, pass through both membrane bilayers and are sites where the INMs and ONMs are fused to each other (Salina et al., 2001; Hetzer et al., 2005; Tran and Wente, 2006). Resident INM proteins pass from the ONM to the INM by diffusion or active transport through the nuclear pores and concentrate in the INM as a result of interactions with the underlying chromatin and the nuclear lamina (Gerace and Burke, 1988; Soullam and Worman, 1995; Ellenberg et al., 1997; Holmer and Worman, 2001; Ohba et al., 2004; Gruenbaum et al., 2005; King et al., 2006). Visualization in living cells has revealed the dynamic nature of the ER network. ER tubules in the periphery of mammalian cells continuously form and fuse, generating a meshwork characterized by the presence of “three-way” junctions between tubules that can move relative to one another (Lee and Chen, 1988; Waterman-Storer and Salmon, 1998; Estrada de Martin et al., 2005). The ER is also structurally reorganized during cell A role for Rab5 in structuring the endoplasmic reticulum
Alkaline Cellulases for Laundry Detergents: Production by Alkalophilic Strains of Bacillus and Some Properties of the Crude Enzymes

Three strains of alkalophilic Bacillus, KSM-19, KSM-64 and KSM-520, were isolated which produced alkaline cellulases suitable as additives for improving the efficiency of detergent products. Their activities were not inhibited at all by metal ions or various components of laundry products, such as surfactants, chelating agents and proteinases. The enzyme preparations showed strong activities toward carboxymethyl cellulose, the optimum pHs being 8.5–9.5 and the optimum temperatures about 50°C.Maximum growth of the isolates was observed at an initial pH of 8.5–9.5; slight growth occurred at neutral pH. Production of the alkaline cellulases required the presence of carboxymethyl cellulose, and it was controlled by a mechanism involving catabolite repression and induction. Two strains, KSM-19 and KSM-64, produced alkaline lichenan-hydrolyzing enzymes.
Effect of breeding for milk yield, diet and management on enteric methane emissions from dairy cows

Enteric methane production from livestock is an important source of anthropogenic greenhouse gas emissions. The aim of the present study was to (1) assess the effect of long-term breeding for kilograms of milk fat plus protein production and (2) investigate the influence of parity, genetic line and diet on predicted enteric methane emissions of Holstein Friesian dairy cows. Analyses were based on 17 years of experimental data for lactating and dry cows, housed and at pasture. Restricted maximum likelihood (REML) was used to assess the effects of parity, genetic line and diet on the predicted enteric methane output of lactating and dry cows. A non-linear equation based on metabolisable energy intake (MEI) was used to predict daily enteric methane output. The present study found that selection for kilograms of milk fat plus protein production, zero-grazing low-forage diets and maintaining persistently high-yielding older cows can reduce a cow’s enteric methane emissions per kilogram milk by up to 12%, on average. Comparing the first 5 years to the most recent 5 years of the study period showed that large savings of 19% and 23% in enteric methane per kilogram milk were made in cows selected for milk fat plus protein or selected to remain close to the average genetic merit for milk fat plus protein production for all animals evaluated in the UK, respectively. Additionally, management to minimise the length of the drying-off period can help reduce enteric methane emissions during a cow’s lactation period.
Dynamics of Myxobolus cerebralis in the Lostine River, Oregon: Implications for Resident and Anadromous Salmonids

Abstract Myxobolus cerebralis, the myxozoan parasite causing whirling disease in salmonids, was first detected in northeastern Oregon in 1986. To better understand the potential impact of M. cerebralis on resident and anadromous salmonids in this region, a series of studies was conducted in the Lostine River, where infected fish were first reported. Rainbow trout Oncorhynchus mykiss fry were exposed in sentinel cages for 14 d at five sites from near the river's mouth to the headwaters during the period from July 1998 to November 1999. A subsample of exposed fry was assayed for the presence of DNA of M. cerebralis by polymerase chain reaction. Following four exposures, fish were held in the laboratory for 5 months of observation. The severity of infection in these fish was determined by histological examination, enumeration of spores isolated from the cranial cartilage, and observation of clinical signs. Sentinel fry became infected throughout the river from March to November, although the prevalence of in.
Acute-on-chronic liver failure syndrome - clinical results from an intensive care unit in a liver transplant center

Objective To characterize a cohort of acute-on-chronic liver failure patients in Intensive Care and to analyze the all-cause 28-day mortality risk factors assessed at ICU admission and day 3. Methods This was a retrospective cohort study of consecutive patients admitted to the intensive care unit between March 2013 and December 2016. Results Seventy-one patients were included. The median age was 59 (51 - 64) years, and 81.7% of patients were male. Alcohol consumption alone (53.5%) was the most frequent etiology of cirrhosis and infection (53.5%) was the most common acute-on-chronic liver failure precipitating event. At intensive care unit admission, the clinical severity scores were APACHE II 21 (16 - 23), CLIF-SOFA 13 (11 - 15), Child-Pugh 12 (10 - 13) and MELD 27 (20 - 32). The acute-on-chronic liver failure scores were no-acute-on-chronic liver failure: 11.3%; one: 14.1%; two: 28.2% and three: 46.5%; and the number of organ failures was one: 4.2%; two: 42.3%; three: 32.4%; four: 16.9%; and five: 4.2%. Liver transplantation was performed in 15.5% of patients. The twenty-eight-day mortality rate was 56.3%, and the in-ICU mortality rate was 49.3%. Organ failure at intensive care unit admission (p = 0.02; OR 2.1; 95%CI 1.2 - 3.9), lactate concentration on day 3 (p = 0.02; OR 6.3; 95%CI 1.4 - 28.6) and the international normalized ratio on day 3 (p = 0.03; OR 10.2; 95%CI 1.3 - 82.8) were independent risk factors. Conclusion Acute-on-chronic liver failure patients presented with high clinical severity and mortality rates. The number of organ failures at intensive care unit admission and the lactate and international normalized ratio on day 3 were independent risk factors for 28-day mortality. We consider intensive care essential for acute-on-chronic liver failure patients and timely liver transplant was vital for selected patients.
In Vitro Nephrotoxicity Induced by Herb-Herb Interaction between Radix Glycyrrhizae and Radix Euphorbiae Pekinensis

Radix Glycyrrhizae (RG)-Radix Euphorbiae Pekinensis (REP) is a representative incompatible herbal pair of Eighteen Incompatible Medicaments (EIM) and has been disputed in clinical application for a long time. The present study was performed with the Madin-Darby canine kidney (MDCK) cell line using cell cytotoxicity assay, apoptosis detection, cell cycle measurement, reactive oxygen species (ROS) determination, and high content analysis (HCA) in combination with high-performance liquid chromatography (HPLC) fingerprint comparison to clarify whether RG and REP can be concomitantly used from the perspective of cytotoxicity, investigate the major correlated compounds, and elucidate the underlying mechanisms. The results showed that the toxicity of REP could be significantly enhanced through its concomitant use with RG in the ratio of 1 : 1, and this increased toxicity could be weakened with the further increased proportion of RG. 3,3′-di-O-methylellagic acid-4′-O-β-D-xylopyranoside (DEAX) and 3,3′-di-O-methylellagic acid (DEA) were shown to be mainly responsible for the toxicity induced by concomitant use of REP and RG. Both RG-REP decoctions and the above two compounds boosted cell apoptosis, cellular morphological change, ROS accumulation, and mitochondrial membrane potential (MMP) disruption. In conclusion, the incompatible use of RG and REP is conditionally established because of the bidirectional regulatory effect of RG, and the major compounds responsible for RG-REP incompatibility are DEAX and DEA, which result in toxicity through activation of mitochondria-dependent apoptosis induced by increased ROS production. This study provided a basis for understanding the incompatible use of RG and REP and the EIM theory.
Lipoprotein Particle Predictors of Arterial Stiffness after 17 Years of Follow Up: The Malmö Diet and Cancer Study

Background Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malmö Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years. Methods Lipoprotein particle analysis was performed on 2,505 men and women from Malmö, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement. Results The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG. Conclusions The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.
Tracking echovirus eleven outbreaks in Guangdong, China: a metatranscriptomic, phylogenetic, and epidemiological study

Abstract In April 2019, a suspect cluster of enterovirus cases was reported in a neonatology department in Guangdong, China, resulting in five deaths. We aimed to investigate the pathogen profiles in fatal cases, the circulation and transmission pattern of the viruses by combining metatranscriptomic, phylogenetic, and epidemiological analyses. Metatranscriptomic sequencing was used to characterize the enteroviruses. Clinical and environmental surveillance in the local population was performed to understand the prevalence and genetic diversity of the viruses in the local population. The possible source(s), evolution, transmission, and recombination of the viruses were investigated by incorporating genomes from the current outbreak, from local retrospective surveillance, and from public databases. Metatranscriptomic analysis identified Echovirus 11 (E11) in three fatal cases. Seroprevalence of neutralization antibody to E11 was 35 to 44 per cent in 3–15 age groups of general population, and the viruses were associated with various clinical symptoms. From the viral phylogeny, nosocomial transmissions were identified and all E11 2019 outbreak strains were closely related with E11 strains circulating in local population 2017–19. Frequent recombination occurred among the 2019 Guangdong E11 outbreak strains and various genotypes in enterovirus B species. This study provides an example of combining advanced genetic technology and epidemiological surveillance in pathogen diagnosis, source(s), and transmission tracing during an infectious disease outbreak. The result highlights the hidden E11 circulation and the risk of viral transmission and infection in the young age population in China. Frequent recombination between Guangdong-like strains and other enterovirus genotypes also implies the prevalence of these emerging E11 strains.
Efficacy of Vitamin E in Methotrexate-Induced Hepatotoxicity in Rheumatoid Arthritis: An Open-Label Case-Control Study

Objective To examine the efficacy of vitamin E in methotrexate- (MTX-) induced transaminitis in patients with rheumatoid arthritis (RA). Methods A case-control study was conducted at a tertiary rheumatology center for 12 months. Patients with RA on MTX and deranged aminotransferases were included. Patients with previous liver diseases, baseline transaminitis before methotrexate initiation, alcohol intake, muscle diseases, under hepatotoxic drugs, and aminotransferases > 3 times the upper normal limit were excluded. The patients were divided into treatment (vitamin E 400 mg bid for 3 months) and control groups (no vitamin E) using a random number table. The dose of MTX was unaltered. Follow-up was done after 3 and 6 months. Independent t-test was done to compare means of two groups. Paired t-test was done to compare differences in mean. Results Among 230 patients, 86.5% were female with a mean BMI of 25.9 ± 4.5 kg/m2. In the treatment group, SGPT and SGOT at baseline were 73.1 ± 20.4 and 60.2 ± 24.5 IU/L, respectively; at 3-month follow-up 44.6 ± 34.2 and 38.3 ± 20.8 IU/L, respectively; and at 6-month follow-up 40.4 ± 35.7 and 34.2 ± 21.9 IU/L, respectively. In the control group, SGPT and SGOT at baseline were 63.4 ± 15.1 and 46.8 ± 13.7 IU/L, respectively, and at 3-month follow-up 55.8 ± 45.9 and 45.5 ± 30.9 IU/L, respectively. Significant decrease in the level of aminotransferases was seen in the treatment group (p value < 0.001) and not in the control group (p values 0.161 and 0.728, respectively). The change in levels of SGPT and SGOT from baseline to 3 months of follow-up was statistically significant in between two study groups (p values 0.007 and <0.001, respectively). From the control group, 29 patients were crossed over to vitamin E for the next 3 months. SGPT and SGOT decreased from 97.6 ± 44.1 to 46.1 ± 40.9 and 69.3 ± 34.9 to 29.1 ± 11.6 IU/L, respectively (p values 0.031 and 0.017, respectively). Conclusion Vitamin E significantly attenuates MTX-induced transaminitis.
Evolution of the Knowledge of Free Radicals and Other Oxidants

Free radicals are chemical species (atoms, molecules, or ions) containing one or more unpaired electrons in their external orbitals and generally display a remarkable reactivity. The evidence of their existence was obtained only at the beginning of the 20th century. Chemists gradually ascertained the involvement of free radicals in organic reactions and, in the middle of the 20th century, their production in biological systems. For several decades, free radicals were thought to cause exclusively damaging effects . This idea was mainly supported by the finding that oxygen free radicals readily react with all biological macromolecules inducing their oxidative modification and loss of function. Moreover, evidence was obtained that when, in the living organism, free radicals are not neutralized by systems of biochemical defences, many pathological conditions develop. However, after some time, it became clear that the living systems not only had adapted to the coexistence with free radicals but also developed methods to turn these toxic substances to their advantage by using them in critical physiological processes. Therefore, free radicals play a dual role in living systems: they are toxic by-products of aerobic metabolism, causing oxidative damage and tissue dysfunction, and serve as molecular signals activating beneficial stress responses. This discovery also changed the way we consider antioxidants. Their use is usually regarded as helpful to counteract the damaging effects of free radicals but sometimes is harmful as it can block adaptive responses induced by low levels of radicals.
Some factors affecting successional change on uranium mine wastes: Insights for ecological restoration

ABSTRACT Question: Are growth form and dispersal-mode replacement during vegetation succession in semi-arid Mediterranean conditions affected by the starting quality of the substrate and by site aspect? Location: Central-western Spain. Methods: We monitored successions on three waste materials left after uranium mining: unbroken waste, broken waste and wastes amended with a sandy material (Arkoses); both north and south aspects were also studied on each substrate. Results: The substrate starting quality had the greatest influence on spontaneous succession, separating the poorer quality substrates (broken and unbroken wastes) from the better ones (Arkoses) and two reference communities (Topsoil and Dehesa). The importance of aspect was confirmed then within each substrate type. Most species with a short life span (mostly annuals and a few biennials), together with some woody species on Arkoses, showed no response to age (years following the deposition of new soil). Others short-lived species declined over time on the poorer wastes but not on the better Arkoses. There was a tendency for life form replacement (from therophytes to hemicryptophytes) during succession only on the poorer-quality substrates. No dispersal-mode replacement sequence was found. Conclusion: Improving the abiotic conditions of the substrate had a great effect on vegetation succession, but this effect was modified by aspect. Aspect took longer to induce differences in floristic composition on the poorer substrates, where succession was slower. Some trends in species responses to successional change were found by considering species traits, particularly life-form. Nomenclature: Tutin et al. (1964–1980).
Evaluation of human epidermal growth factor receptor 2 status of breast cancer using preoperative multidetector computed tomography with deep learning and handcrafted radiomics features

Objective To evaluate the human epidermal growth factor receptor 2 (HER2) status in patients with breast cancer using multidetector computed tomography (MDCT)-based handcrafted and deep radiomics features. Methods This retrospective study enrolled 339 female patients (primary cohort, n=177; validation cohort, n=162) with pathologically confirmed invasive breast cancer. Handcrafted and deep radiomics features were extracted from the MDCT images during the arterial phase. After the feature selection procedures, handcrafted and deep radiomics signatures and the combined model were built using multivariate logistic regression analysis. Performance was assessed by measures of discrimination, calibration, and clinical usefulness in the primary cohort and validated in the validation cohort. Results The handcrafted radiomics signature had a discriminative ability with a C-index of 0.739 [95% confidence interval (95% CI): 0.661−0.818] in the primary cohort and 0.695 (95% CI: 0.609−0.781) in the validation cohort. The deep radiomics signature also had a discriminative ability with a C-index of 0.760 (95% CI: 0.690−0.831) in the primary cohort and 0.777 (95% CI: 0.696−0.857) in the validation cohort. The combined model, which incorporated both the handcrafted and deep radiomics signatures, showed good discriminative ability with a C-index of 0.829 (95% CI: 0.767−0.890) in the primary cohort and 0.809 (95% CI: 0.740−0.879) in the validation cohort. Conclusions Handcrafted and deep radiomics features from MDCT images were associated with HER2 status in patients with breast cancer. Thus, these features could provide complementary aid for the radiological evaluation of HER2 status in breast cancer.
Hunt for Starspots in HARPS Spectra of G and K Stars

We present a method for detecting starspots on cool stars using the cross-correlation function (CCF) of high-resolution molecular spectral templates applied to archival high-resolution spectra of G and K stars observed with the High Accuracy Radial Velocity Planet Searcher (HARPS)/HARPS-N. We report nondetections of starspots on the Sun even when the Sun was spotted, the solar twin 18 Scorpii, and the very spotted Sun-like star HAT-P-11, suggesting that Sun-like starspot distributions will be invisible to the CCF technique, and should not produce molecular absorption signals that might be confused for signatures of exoplanet atmospheres. We detect strong TiO absorption in the T Tauri K-dwarfs LkCa 4 and AA Tau, consistent with significant coverage by cool regions. We show that despite the nondetections, the technique is sensitive to relatively small spot coverages on M dwarfs and large starspot areas on Sun-like stars.