Miracle-dz/UniFAR-FTUs huggingface dataset:
The Cytoplasmic Tail of FPC Antagonizes the Full-Length Protein in the Regulation of mTOR Pathway

FPC (fibrocystin or polyductin) is a single transmembrane receptor-like protein, responsible for the human autosomal recessive polycystic kidney disease (ARPKD). It was recently proposed that FPC undergoes a Notch-like cleavage and subsequently the cleaved carboxy(C)-terminal fragment translocates to the nucleus. To study the functions of the isolated C-tail, we expressed the intracellular domain of human FPC (hICD) in renal epithelial cells. By 3-dimensional (3D) tubulogenesis assay, we found that in contrast to tubule-like structures formed from control cells, hICD-expressing cells exclusively formed cyst-like structures. By western blotting, we showed that the Akt/mTOR pathway, indicated by increased phosphorylation of Akt at serine 473 and S6 kinase 1 at threonine 389, was constitutively activated in hICD-expressing cells, similar to that in FPC knockdown cells and ARPKD kidneys. Moreover, application of mTOR inhibitor rapamycin reduced the size of the cyst-like structures formed by hICD-expressing cells. Application of either LY294002 or wortmannin inhibited the activation of both S6K1 and Akt. Expression of full-length FPC inhibited the activation of S6 and S6 kinase whereas co-expression of hICD with full-length FPC antagonized the inhibitory effect of full-length FPC on mTOR. Taken together, we propose that FPC modulates the PI3K/Akt/mTOR pathway and the cleaved C-tail regulates the function of the full-length protein.
Process modeling, synthesis and thermodynamic evaluation of hydrogen production from hydrothermal processing of lipid extracted algae integrated with a downstream reformer conceptual plant

ABSTRACT Hydrothermal processing of organics, particularly the supercritical water gasification process, has showed potential in lab-scale records to valorize the chemical energy stored in biomass. The technology manipulates the varying thermo-physical properties around the critical point of water to convert and upgrade the organic content, as well as extract inorganics. This study provides a systematic evaluation to the process upscaling into energetically efficient commercial demonstration. Conceptual plant flowsheets for a lipid extracted algae feedstock were developed on Aspen plus® for 99.9% purity hydrogen fuel production. The advantageous reactor system configuration is integrated within a layout that includes subsequent power generation and gas purification. The process is coupled with a downstream steam reformer block to maximize the poly-generation of hydrogen fuel, power and thermal heat. To thermodynamically evaluate the plant designs, minimum process utility demands were computed with the pinch analysis method, and different energy recovery scenarios, as well as alternative design configurations for optimal heat recovery were assessed. Finally, a comparative assessment showed that integrating downstream steam reforming with hydrothermal processing lead to an increase in the overall energetic efficiency from 34.2 to 46.2%, in the fuel-equivalent efficiency from 44.1 to 55% and exergetic efficiency from 28.9 to 41.4%.
Growth patterns and their implications for preterm infants in a culture of rapid modernization

This prospective longitudinal study explored the growth patterns of preterm infants and the implications of rearing them in an advancing culture. The study measured the weight, length, and head circumference of 343 Korean preterm infants over 12 months corrected age. Data were analyzed using a generalized estimation equation for growth patterns of preterm infants by the degree of prematurity (mild, moderate, or severe). Results showed that the early ‘catch-up phenomenon’, accelerated growth rate, occurred around 11 months corrected age, although the mild preterm group weighed less, was shorter, and had a smaller head circumference than the moderate and severe preterm groups. This may reflect the Asian culture’s preference for big babies and draws special attention to the influence of cultural values and childrearing practices in the growth of preterm infants. Pediatric nurses should be alert to accelerated growth in preterm infants in societies in cultural transition.
Beyond These Walls: Can Psychosocial Clubhouses Promote the Social Integration of Adults With Serious Mental Illness in the Community?

Objective: The study examined factors associated with community integration experiences of adults with serious mental illness who were members of psychosocial rehabilitation clubhouses in New York City. Method: Ninety-two clubhouse members completed an online survey. The study examined relative contribution of adults’ reports of individual factors (self-reported psychiatric symptoms, self-esteem), community supports (self-reported employment status and perceived family support), and the clubhouse environment (self-reported time spent in the clubhouse, clubhouse supportiveness, and practical orientation) in accounting for variation in members’ reports of social integration within the clubhouse and within the larger community. Results: Hierarchical linear regression results suggest a differential pattern of variables associated with participants’ experience of social integration within the clubhouse versus outside the clubhouse with the larger non-mental-health consumers. Adults’ reports of more time spent in the clubhouse and perceptions of clubhouse environment as having a more practical orientation were associated with adults’ reports of greater social integration within the clubhouse. In contrast, greater self-esteem and being independently employed were associated with greater social integration outside the clubhouse. Perceived family support was associated with higher levels of social integration both within and outside the clubhouse setting. Conclusion and Implication for Practice: Greater social integration of clubhouse members both in and outside the clubhouse environment is essential in understanding community integration. Recommendations for the clubhouse model to improve community integration experiences of its members are discussed.
Regulator of G Protein Signaling 6 Protects the Heart from Ischemic Injury

Gαi-coupled receptors play important roles in protecting the heart from ischemic injury. Regulator of G protein signaling (RGS) proteins suppress Gαi signaling by accelerating the GTPase activity of Gαi subunits. However, the roles of individual RGS proteins in modulating ischemic injury are unknown. In this study, we investigated the effect of RGS6 deletion on myocardial sensitivity to ischemic injury. Hearts from RGS6 knockout (RGS6−/−) and RGS6 wild-type (RGS6+/+) mice were subjected to 30 minutes of ischemia and 2 hours of reperfusion on a Langendorff heart apparatus. Infarcts in RGS6−/− hearts were significantly larger than infarcts in RGS6+/+ hearts. RGS6−/− hearts also exhibited increased phosphorylation of β2-adrenergic receptors and G protein–coupled receptor kinase 2 (GRK2). Mitochondrial GRK2 as well as caspase-3 cleavage were increased significantly in RGS6−/− hearts compared with RGS6+/+ hearts after ischemia. Chronic propranolol treatment of mice prevented the observed increases in ischemic injury and the GRK2 phosphorylation observed in RGS6−/− hearts. Our findings suggest that loss of RGS6 predisposes the ventricle to prodeath signaling through a β2AR-GRK2–dependent signaling mechanism, and they provide evidence for a protective role of RGS6 in the ischemic heart. Individuals expressing genetic polymorphisms that suppress the activity of RGS6 may be at increased risk of cardiac ischemic injury. Furthermore, the development of agents that increase RGS6 expression or activity might provide a novel strategy for the treatment of ischemic heart disease.
Environmental Validation of Legionella Control in a VHA Facility Water System

OBJECTIVES We conducted this study to determine what sample volume, concentration, and limit of detection (LOD) are adequate for environmental validation of Legionella control. We also sought to determine whether time required to obtain culture results can be reduced compared to spread-plate culture method. We also assessed whether polymerase chain reaction (PCR) and in-field total heterotrophic aerobic bacteria (THAB) counts are reliable indicators of Legionella in water samples from buildings. DESIGN Comparative Legionella screening and diagnostics study for environmental validation of a healthcare building water system. SETTING Veterans Health Administration (VHA) facility water system in central Texas. METHODS We analyzed 50 water samples (26 hot, 24 cold) from 40 sinks and 10 showers using spread-plate cultures (International Standards Organization [ISO] 11731) on samples shipped overnight to the analytical lab. In-field, on-site cultures were obtained using the PVT (Phigenics Validation Test) culture dipslide-format sampler. A PCR assay for genus-level Legionella was performed on every sample. RESULTS No practical differences regardless of sample volume filtered were observed. Larger sample volumes yielded more detections of Legionella. No statistically significant differences at the 1 colony-forming unit (CFU)/mL or 10 CFU/mL LOD were observed. Approximately 75% less time was required when cultures were started in the field. The PCR results provided an early warning, which was confirmed by spread-plate cultures. The THAB results did not correlate with Legionella status. CONCLUSIONS For environmental validation at this facility, we confirmed that (1) 100 mL sample volumes were adequate, (2) 10× concentrations were adequate, (3) 10 CFU/mL LOD was adequate, (4) in-field cultures reliably reduced time to get results by 75%, (5) PCR provided a reliable early warning, and (6) THAB was not predictive of Legionella results. Infect Control Hosp Epidemiol 2018;39:259–266
An investigation of morphological awareness and processing in adults with low literacy

Morphological awareness, which is an understanding of how words can be broken down into smaller units of meaning such as roots, prefixes, and suffixes, has emerged as an important contributor to word reading and comprehension skills. The first aim of the current study was to investigate the contribution of morphological awareness independent of phonological awareness and decoding to the reading comprehension abilities of adults with low literacy. Results indicated that morphological awareness was a significant unique predictor of reading comprehension. A second aim of the study was to investigate the processing of morphologically complex words of adults with low literacy in both an oral reading passage and a single-word naming task. Adults’ accuracy and response times were measured on different types of morphologically complex words and compared with control words matched on frequency in both the passage and the naming tasks. Results revealed that adults were vulnerable to morphological complexity: they performed more accurately and faster on matched control words versus morphologically complex word types. The educational implications for Adult Basic Education programs are discussed.
Effect of Additional Treatments Combined with Conventional Therapies in Pregnant Patients with High-Risk Antiphospholipid Syndrome: A Multicentre Study

Abstract The effect of additional treatments combined with conventional therapy on pregnancy outcomes was examined in high-risk primary antiphospholipid syndrome (PAPS) patients to identify the most effective treatment strategy. The study's inclusion criteria were (1) positivity to lupus anticoagulant alone or associated with anticardiolipin and/or anti-β2 glycoprotein I antibodies; (2) a history of severe maternal–foetal complications (Group I) or a history of one or more pregnancies refractory to conventional therapy leading to unexplained foetal deaths not associated with severe maternal–foetal complications (Group II). Two different additional treatments were considered: oral—low-dose steroids (10–20 mg prednisone daily) and/or 200 to 400 mg daily doses of hydroxychloroquine and parenteral—intravenous immunoglobulins at 2 g/kg per month and/or plasma exchange. The study's primary outcomes were live birth rates and pregnancy complications. A total of 194 pregnant PAPS patients attending 20 tertiary centres were retrospectively enrolled. Hydroxychloroquine was found to be linked to a significantly higher live birth rate with respect to the other oral treatments in the Group II patients. The high (400 mg) versus low (200 mg) doses of hydroxychloroquine (p = 0.036) and its administration before versus during pregnancy (p = 0.021) were associated with a significantly higher live birth rate. Hydroxychloroquine therapy appeared particularly efficacious in the PAPS patients without previous thrombosis. Parenteral treatments were associated with a significantly higher live birth rate with respect to the oral ones (p = 0.037), particularly in the Group I patients. In conclusion, some additional treatments were found to be safe and efficacious in high-risk PAPS pregnant women.
Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria

Horizontal gene transfer (HGT) plays a central role in bacterial evolution, yet the molecular and cellular constraints on functional integration of the foreign genes are poorly understood. Here we performed inter-species replacement of the chromosomal folA gene, encoding an essential metabolic enzyme dihydrofolate reductase (DHFR), with orthologs from 35 other mesophilic bacteria. The orthologous inter-species replacements caused a marked drop (in the range 10-90%) in bacterial growth rate despite the fact that most orthologous DHFRs are as stable as E.coli DHFR at 37° C and are more catalytically active than E. coli DHFR. Although phylogenetic distance between E. coli and orthologous DHFRs as well as their individual molecular properties correlate poorly with growth rates, the product of the intracellular DHFR abundance and catalytic activity (kcat/KM), correlates strongly with growth rates, indicating that the drop in DHFR abundance constitutes the major fitness barrier to HGT. Serial propagation of the orthologous strains for ∼600 generations dramatically improved growth rates by largely alleviating the fitness barriers. Whole genome sequencing and global proteome quantification revealed that the evolved strains with the largest fitness improvements have accumulated mutations that inactivated the ATP-dependent Lon protease, causing an increase in the intracellular DHFR abundance. In one case DHFR abundance increased further due to mutations accumulated in folA promoter, but only after the lon inactivating mutations were fixed in the population. Thus, by apparently distinguishing between self and non-self proteins, protein homeostasis imposes an immediate and global barrier to the functional integration of foreign genes by decreasing the intracellular abundance of their products. Once this barrier is alleviated, more fine-tuned evolution occurs to adjust the function/expression of the transferred proteins to the constraints imposed by the intracellular environment of the host organism.
The chemistry of extragalactic carbon stars

Prompted by the ongoing interest in Spitzer Infrared Spectrometer spectra of carbon stars in the Large Magellanic Cloud, we have investigated the circumstellar chemistry of carbon stars in low-metallicity environments. Consistent with observations, our models show that acetylene is particularly abundant in the inner regions of low metallicity carbon-rich asymptotic giant branch stars – more abundant than carbon monoxide. As a consequence, larger hydrocarbons have higher abundances at the metallicities of the Magellanic Clouds than in stars with solar metallicity. We also find that the oxygen and nitrogen chemistry is suppressed at lower metallicity, as expected. Finally, we calculate molecular line emission from carbon stars in the Large and Small Magellanic Cloud and find that several molecules should be readily detectable with the Atacama Large Millimeter Array at Full Science operations.
Tolerance to Stress Combination in Tomato Plants: New Insights in the Protective Role of Melatonin

Abiotic stresses such as drought, heat or salinity are major causes of yield loss worldwide. Recent studies have revealed that the acclimation of plants to a combination of different environmental stresses is unique and therefore cannot be directly deduced from studying the response of plants to each of the different stresses applied individually. The efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Here, we report on the role of melatonin in the protection of the photosynthetic apparatus through the increase in ROS detoxification in tomato plants grown under the combination of salinity and heat, two of the most common abiotic stresses known to act jointly. Plants treated with exogenous melatonin showed a different modulation in the expression on some antioxidant-related genes and their related enzymes. More specifically, ascorbate peroxidase, glutathione reductase, glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase (APX, GR, GPX and Ph-GPX, resepctively) showed an antagonistic regulation as compared to plants that did not receive melatonin. This translated into a better antioxidant capacity and to a lesser ROS accumulation under stress combination. The performance of the photosynthesis parameters and the photosystems was also increased in plants treated with exogenous melatonin under the combination of salinity and heat. In accordance with these findings, tomato plants treated with melatonin were found to grow better under stress combination that the non-treated ones. Our study highlights the important role that exogenous melatonin plays in the acclimation of plants to a combination of two different abiotic stresses, and how this compound can specifically regulate oxidative stress-related genes and enzymes to increase plant tolerance.
Overexpression of Receptor Tyrosine Kinase EphB4 Triggers Tumor Growth and Hypoxia in A375 Melanoma Xenografts: Insights from Multitracer Small Animal Imaging Experiments ‡

Experimental evidence has associated receptor tyrosine kinase EphB4 with tumor angiogenesis also in malignant melanoma. Considering the limited in vivo data available, we have conducted a systematic multitracer and multimodal imaging investigation in EphB4-overexpressing and mock-transfected A375 melanoma xenografts. Tumor growth, perfusion, and hypoxia were investigated by positron emission tomography. Vascularization was investigated by fluorescence imaging in vivo and ex vivo. The approach was completed by magnetic resonance imaging, radioluminography ex vivo, and immunohistochemical staining for blood and lymph vessel markers. Results revealed EphB4 to be a positive regulator of A375 melanoma growth, but a negative regulator of tumor vascularization. Resulting in increased hypoxia, this physiological characteristic is considered as highly unfavorable for melanoma prognosis and therapy outcome. Lymphangiogenesis, by contrast, was not influenced by EphB4 overexpression. In order to distinguish between EphB4 forward and EphrinB2, the natural EphB4 ligand, reverse signaling a specific EphB4 kinase inhibitor was applied. Blocking experiments show EphrinB2 reverse signaling rather than EphB4 forward signaling to be responsible for the observed effects. In conclusion, functional expression of EphB4 is considered a promising differentiating characteristic, preferentially determined by non-invasive in vivo imaging, which may improve personalized theranostics of malignant melanoma.
Use of leadless pacemakers in Europe: results of the European Heart Rhythm Association survey

The purpose of this European Heart Rhythm Association (EHRA) survey is to provide an overview of the current use of leadless pacemakers (LLPM) across a broad range of European centres. An online questionnaire was sent to centres participating in the EHRA Electrophysiology Research Network. Questions dealt with standards of care and policies used for patient management, indications, and techniques of implantation of LLPM. In total, 52 centres participated in the survey. Most (86%) reported using LLPM, although 82% of these centres implanted <30 LLPM devices during the last 12 months. Non-availability (36%), lack of reimbursement (55%), and cost of the device (91%) were factors limiting the use of LLPM. The most commonly reported indications for LLPM were permanent atrial fibrillation (83%), a history of complicated conventional pacemaker (87%), or an anticipated difficult vascular access (91%). Implantation of LLPM is perceived as an easy-to-do and safe procedure by most implanters (64%), while difficult or risky in 28%, and comparable to conventional pacemakers by only a few (8%). Local vascular complications were the most frequently reported major problems (28%), but a significant number of respondents (36%) have never encountered any issue after LLPM implantation. Although cost and reimbursement issues strongly influence the use of LLPM, most respondents (72%) anticipate a significant increase in device utilization within next 2 years.
Response of saliva Na/K ratio to changing Na supply of lactating cows under tropical conditions.

BACKGROUND Factorial determination of the sodium (Na) requirement of heat-stressed lactating cows is hindered by accurate estimates of the Na losses through sweat. Direct studies, therefore, may be needed requiring information on the time course of healthy animals to become Na depleted and the subsequent rate of repletion. The rate of Na depletion and subsequent rate of Na repletion with two levels of dietary Na to lactating dairy cows housed under tropical conditions were investigated using the salivary Na/K. RESULTS The 12 lactating cows (salivary Na/K ratio 14.6) rapidly developed clinical signs of Na deficiency, including pica, polyuria and polydipsia, reduced body weight and reduced milk yield when fed a low-Na ration (0.33 g kg-1 dry matter (DM)) for 3 weeks. Deficiency symptoms were associated with a rapid decrease in salivary Na/K ratio to <4.3 from 7 to 21 days. Subsequent repletion of the cows with NaCl to a ration concentration of 1.1 or 1.6 g Na kg-1 DM for 5 weeks did not restore salivary Na/K ratio to values of >6. CONCLUSION A daily Na intake of heat-stressed lactating cows to a ration intake of 1.6 g Na kg-1 DM was insufficient to restore Na deficiency. One week was sufficient to deplete heat-stressed lactating cows of Na, allowing for rapid dose-response studies utilizing the salivary Na/K ratio as a parameter for Na status of cows under tropical conditions. © 2016 Society of Chemical Industry.