Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct Kinetic and Spatial Patterns of Protein Kinase C (PKC)- and Epidermal Growth Factor Receptor (EGFR)-dependent Activation of Extracellular Signal-regulated Kinases 1 and 2 by Human Nicotinic Acid Receptor GPR109A*

Nicotinic acid (niacin) has been widely used as a lipid-lowering drug for several decades, and recently, orphan G protein-coupled receptor GPR109A has been identified as a receptor for niacin. Mechanistic investigations have shown that, upon niacin activation, GPR109A couples to a Gi protein and inhibits adenylate cyclase activity, leading to inhibition of liberation of free fatty acid. However, the underlying molecular mechanisms for GPR109A signaling remain largely unknown. Using CHO-K1 cells stably expressing GPR109A and A431 cells, which are a human epidermoid cell line with high levels of endogenous expression of functional GPR109A receptors, we found that activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) by niacin was rapid, peaking at 5 min, and was significantly blocked by pertussis toxin. Furthermore, time course experiments with different kinase inhibitors demonstrated that GPR109A induced ERK1/2 activation via the matrix metalloproteinase/epidermal growth factor receptor transactivation pathway at both early and later time points (2–5 min); this pathway was distinct from the PKC pathway-mediated ERK1/2 phosphorylation that occurs at early time points (≤2 min) in response to niacin. Overexpression of Gβγ subunit scavengers βARK1-CT and the Gα subunit of transducin led to a significant reduction of ERK1/2 phosphorylation, suggesting a critical role for βγ subunits in GPR109A-activated ERK1/2 phosphorylation. Using arrestin-2/3-specific siRNA and an internalization-deficient GPR109A mutant, we found that arrestin-2 and arrestin-3 were not involved in GPR109A-mediated ERK1/2 activation. In conclusion, our findings demonstrate that upon binding to niacin GPR109A receptors initially activate Gi, leading to dissociation of the Gβγ subunit from activated Gi, and subsequently induce ERK1/2 activation via two distinct pathways, one PKC-dependent pathway occurring at a peak time of ≤2 min and the other matrix metalloproteinase-dependent growth factor receptor transactivation occurring at both early and later time points (2–5 min).
Building Up of the Plastid Transcriptional Machinery during Germination and Early Plant Development1

The plastid genome is transcribed by three different RNA polymerases, one is called plastid-encoded RNA polymerase (PEP) and two are called nucleus-encoded RNA polymerases (NEPs). PEP transcribes preferentially photosynthesis-related genes in mature chloroplasts while NEP transcribes preferentially housekeeping genes during early phases of plant development, and it was generally thought that during plastid differentiation the building up of the NEP transcription system precedes the building up of the PEP transcription system. We have now analyzed in detail the establishment of the two different transcription systems, NEP and PEP, during germination and early seedling development on the mRNA and protein level. Experiments have been performed with two different plant species, Arabidopsis (Arabidopsis thaliana) and spinach (Spinacia oleracea). Results show that the building up of the two different transcription systems is different in the two species. However, in both species NEP as well as PEP are already present in seeds, and results using Tagetin as a specific inhibitor of PEP activity demonstrate that PEP is important for efficient germination, i.e. PEP is already active in not yet photosynthetically active seed plastids.
Congestive Heart Failure and Chronic Obstructive Pulmonary Disease Predict Poor Surgical Outcomes in Older Adults Undergoing Elective Diverticulitis Surgery

BACKGROUND: Diverticulitis is a common medical condition that disproportionately affects older adults. The ideal management of recurrent diverticulitis, including the role of prophylactic colectomy, remains uncertain. OBJECTIVE: This study aimed to investigate the outcomes among older patients undergoing elective surgery for diverticulitis and examine subgroups of patients with comorbid congestive heart failure and chronic obstructive pulmonary disease to determine whether outcomes in these patients are worse than in other groups. DESIGN: This article reports a retrospective cohort study of patients undergoing elective surgery for diverticulitis. SETTING: Data were derived from the 100% Medicare Provider Analysis and Review inpatient files from 2004 to 2007. PATIENTS: Included were 22,752 patients, age 65 years and older, with a primary diagnosis of diverticulitis that underwent elective left-colon resection, colostomy, or ileostomy. MAIN OUTCOME MEASURE: The primary outcome measure was in-hospital mortality. The secondary outcome measures were intestinal diversion rates (colostomy and ileostomy) and postoperative complications. RESULTS: Overall mortality, intestinal diversion (colostomy and ileostomy), and postoperative complication rate were 1.2%, 11.3%, and 22.1%. Patients with congestive heart failure had increased odds of in-hospital mortality (OR 3.5, 95% CI 2.59–4.63), colostomy (OR 1.9, 95% CI 1.69–2.27), and all postoperative complications, including hemorrhagic (OR 1.5, 95% CI 1.01–2.11), wound (OR 1.9, 95% CI 1.50–2.39), pulmonary (OR 4.2, 95% CI 3.59–4.85), cardiac (OR 4.6, 95% CI 3.68–5.74), postoperative shock/sepsis (OR 3.2, 95% CI 2.53–4.35), renal (OR 4.1, 95% CI 3.22–5.12), and thromboembolic (OR 1.6, 95% CI 1.00–2.43) complications. Patients with chronic obstructive pulmonary disease had significantly increased odds of wound (OR 1.4, 95% CI 1.19–1.67) and pulmonary (OR 2.2, 95% CI 1.94–2.50) complications. Advancing age, congestive heart failure, and chronic obstructive pulmonary disease were significantly associated with increased morbidity and mortality. LIMITATIONS: Medicare data are limited by the potential for lack of generalizability to patients <65 years and the potential for coding errors. CONCLUSIONS: Elective diverticular surgery in older patients carries substantial morbidity, especially in those patients with comorbid congestive heart failure and chronic obstructive pulmonary disease. The rate of perioperative complications that we document in this patient population may attenuate some of the expected benefit of surgery.
Formins: signaling effectors for assembly and polarization of actin filaments

Eukaryotic cells require filamentous actin to maintain their shape and for movement, growth and replication. New actin filaments are formed by the cutting of existing filaments or de novo through the action of specialized nucleators. The most highly characterized nucleator is the Arp2/3 complex, which nucleates the branched actin networks in the lamellae of migrating cells. Recently, Bni1p, which is a member of the formin family of proteins, has been shown to nucleate actin filaments in vitro. Formins are implicated in the formation of actin cables in yeast, stress fibers in tissue culture cells and cytokinesis in many cell types. Formins contain two highly conserved formin-homology domains, FH1 and FH2. The Bni1p FH2 domain is sufficient to mediate nucleation. The Bni1p FH1 domain binds profilin, an actin-monomer-binding protein that delivers actin to the growing barbed end of filaments. The Bni1p FH1-profilin interaction enhances nucleation. Formins participate in a number of signaling pathways that control the assembly of specific actin structures and bind the barbed end of actin filaments, thereby providing a cytoskeletal basis for the establishment of cell polarity.
LIFE‐HISTORY EVOLUTION IN GUPPIES: 2. REPEATABILITY OF HELD OBSERVATIONS AND THE EFFECTS OF SEASON ON LIFE HISTORIES

Natural populations of guppies that co‐occur with the pike cichlid Crenicichla alta and associated predators mature at smaller body sizes, produce more and smaller offspring per litter reproduce more frequently, and have higher reproductive allotments (weight of developing embryos/total body weight) than guppies that co‐occur with just the killifish Rivulus harti (Reznick and Endler, 1982). I here consider three forms of repeatability in these life‐history patterns: i) among replicate samples collected on the same day from the same locality, ii) between Crenicichla and Rivulus communities among a new series of localities, and iii) among a smaller series of Crenicichla and Rivulus localities sampled in two wet and two dry seasons.
Modern management of uterine fibroids

Uterine fibroids are the most common tumor of the reproductive tract in women of reproductive age. Although they are benign tumors that are often asymptomatic, uterine fibroids may cause debilitating symptoms in many women, such as abnormal uterine bleeding, abdominal pain, increased abdominal girth, urinary frequency, constipation, pregnancy loss, dyspareunia, and in some cases infertility. Several approaches are available for the treatment of uterine fibroids. These include pharmacologic options, such as hormonal therapies and gonadotropin‐releasing hormone agonists; surgical approaches, such as hysterectomy, myomectomy, myolysis, laparoscopic uterine artery occlusion, magnetic resonance imaging‐guided focused ultrasound surgery, and uterine artery embolization. The choice of approach may be dictated by factors such as the patient's desire to become pregnant in the future, the importance of uterine preservation, symptom severity, and tumor characteristics. New treatment options for uterine fibroids would be minimally invasive, have long‐term data demonstrating efficacy and safety, have minimal or no incidence of fibroid recurrence, be easy to perform, preserve fertility, and be cost effective. New treatment approaches are under investigation, with the goals of being effective, safe, and less invasive.
Influence Prediction of Injury and Vibration on Adjacent Components of Spine Using Finite Element Methods

Objectives A three-dimensional finite element (FE) model of the lumbar spine L3–L5 segment, the ligaments of which were assumed to be nonlinear materials, was established based on the actual vertebra geometry to investigate the influence of the injury lumbar spine on its adjacent components on the condition of whole-body vibration. Several injury conditions of the spine components were assumed, such as facetectomy, nucleotomy, and removal of bony posterior elements. Methods The dynamic FE analyses were carried out for those FE conditions under cyclic compression loads at the frequencies of 5 and 10 Hz. Then a comparison between the dynamic results and the static results was conducted to analyze the influence of both the nucleus injury and the facet joint injury on the adjacent intervertebral discs. Results and Conclusions The results indicate that the lumbar spine exhibits not only vertical vibration but also the flexion—extension motion during vibration. The denucleation will cause high stress and large disc bulge on the disc annulus under vibration. The facet joints of lumbar spine can limit the motion amplitude of flexion—extension and protect both the posterior regions and the posterolateral regions of disc annulus from large strain and stress during vibration. The facet joint removal will increase the stress of disc annulus by around 15% at the posterior region for the conditions of nucleotomy or no vibration. The stress of annulus circumference is higher at the posterolateral region than that of other regions of annulus circumference, and the facet joint removal may exacerbate the intervertebral disc degeneration on the condition of whole-body vibration.
Streptococcus faecalis R plasmid pJH1 contains a pAM alpha 1 delta 1-like replicon

Streptococcus faecalis R plasmid pJH1 did not transform competent strains of Streptococcus sanguis. A hybrid plasmid, pDL310, consisting of virtually all of the S. faecalis hemolysin-bacteriocin plasmid pJH2 and a segment of pJH1 DNA that included the tetracycline resistance determinant, yielded tetracycline-resistant transformants at a frequency of less than 10(-8) transformants per CFU, when it was added to a competent culture of S. sanguis Wicky. Four of the transformants contained a 4.7-kilobase plasmid (pDL316) that transformed strain Wicky at a frequency of 8.6 X 10(-8). Restriction endonuclease digests, agarose gel electrophoresis, and Southern blot hybridizations indicated that pDL316 consisted entirely of pJH1-derived DNA. Additional restriction studies, Southern blot hybridizations, and heteroduplex analyses indicated that pDL316 was very closely related to 4.6-kilobase tetracycline resistance plasmid pAM alpha 1 delta 1, a derivative of 9.0-kilobase S. faecalis plasmid pAM alpha 1.
An evaluation of the Charlson co-morbidity score for predicting sepsis after elective major surgery

Background and Aims: Severe sepsis is a significant cause of morbidity and mortality following major surgery. The Charlson co-morbidity score (CCS) has been shown to be associated with severe sepsis following major surgery for cancer. This prospective observational study investigated the effect of patient factors (CCS, gender, age and malignancy) and intraoperative factors (duration of surgery and allogeneic blood transfusion) on the incidence of sepsis after elective major surgery, and the impact of patient co-morbidities on length of stay in critical care. Materials and Methods: We prospectively identified a cohort of 101 patients undergoing elective major surgery in a university teaching hospital. The CCS was calculated before surgery, and the incidence of sepsis was documented following surgery. We investigated whether age, malignancy, intraoperative allogeneic blood transfusion, length of surgery or gender were associated with sepsis following surgery. Results: Twenty-seven (27%) patients developed sepsis. Using multivariate logistic regression, the duration of surgery was associated with the development of sepsis after surgery (P = 0.054, odds ratio 1.2). The CCS was not associated with sepsis in this population of cancer and non-cancer patients undergoing elective major surgery, but was associated with longer length of stay in the intensive care unit (P = 0.016). Conclusions: Duration of surgery, but not patient co-morbidity as assessed by the CCS, may predict the postoperative incidence of sepsis. CCS could be used as a guide to predict consumption of critical care resources by elective surgical patients. A higher CCS was associated with a longer ICU stay. Resources, such as postoperative goal directed therapy, may be useful in reducing length of stay, hospital costs and risks of infective complications in this subgroup of patients with higher CCS.
Determinantal Point Processes in Randomized Numerical Linear Algebra

Randomized Numerical Linear Algebra (RandNLA) uses randomness to develop improved algorithms for matrix problems that arise in scientific computing, data science, machine learning, etc. Determinantal Point Processes (DPPs), a seemingly unrelated topic in pure and applied mathematics, is a class of stochastic point processes with probability distribution characterized by sub-determinants of a kernel matrix. Recent work has uncovered deep and fruitful connections between DPPs and RandNLA which lead to new guarantees and improved algorithms that are of interest to both areas. We provide an overview of this exciting new line of research, including brief introductions to RandNLA and DPPs, as well as applications of DPPs to classical linear algebra tasks such as least squares regression, low-rank approximation and the Nystrom method. For example, random sampling with a DPP leads to new kinds of unbiased estimators for least squares, enabling more refined statistical and inferential understanding of these algorithms; a DPP is, in some sense, an optimal randomized algorithm for the Nystrom method; and a RandNLA technique called leverage score sampling can be derived as the marginal distribution of a DPP. We also discuss recent algorithmic developments, illustrating that, while not quite as efficient as standard RandNLA techniques, DPP-based algorithms are only moderately more expensive.
Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis

Expression of mRNAs coding for the ACTH secretagogues corticotropin- releasing factor (CRF) and arginine vasopressin (AVP) was examined in the hypothalamic paraventricular nucleus (PVN) of rats bearing hippocampal lesions. Either total hippocampectomy (HPX) or extirpation of the dorsal hippocampus (DHPX) precipitated a 4-fold increase in CRF mRNA expression relative to sham-operated controls (SHAM), as determined by semiquantitative in situ hybridization histochemistry. AVP mRNA was localized to individual parvocellular neurons of the medial parvocellular division of the PVN in only the HPX and DHPX groups, consistent with enhanced production of AVP message in this neuronal population subsequent to hippocampal damage. HPX did not affect AVP mRNA content in magnocellular divisions of PVN. Plasma beta- endorphin levels were significantly elevated in the HPX and DHPX groups relative to SHAM animals, indicating a chronic increase in release of proopiomelanocortin peptides from the anterior pituitary gland in response to hippocampal lesion. Circulating corticosterone levels were elevated in HPX rats as well. To control for effects of lesion size and location, additional animals received large ablations of cerebral cortex or cerebellum. In neither case was CRF or AVP mRNA significantly altered in the PVN. The results suggest that the hippocampus exercises a tonic inhibitory role on ACTH secretagogue production in neuroendocrine neurons promoting ACTH release.
Enumeration of micro-organisms in food: a comparative study of five methods

SUMMARY Five methods for the enumeration of micro-organisms in food (pour plate, surface spread plate, surface drop, agar droplet, and microdilution) were used in parallel to examine 100 samples selected from a wide range of food products. Statistical analyses of the results showed that the regression and correlation coefficients between the methods were highly significant; the lowest correlation coefficient derived for any pair of methods was 0·979. A variation in count between the methods of less than 0·5 log10 cycles was given by 98% of the samples. Analysis of the operation times and material requirements of each method showed that substantial savings in cost, time, space and support labour were achieved with the microdilution and agar droplet techniques as compared with the conventional pour plate and spread plate methods.
Molecular Evolution of Hepatitis B Virus over 25 Years

ABSTRACT Determining the longitudinal molecular evolution of hepatitis B virus (HBV) is difficult due to HBV's genomic complexity and the need to study paired samples collected over long periods of time. In this study, serial samples were collected from eight hepatitis B virus e antigen-negative asymptomatic carriers of HBV genotype B in 1979 and 2004, thus providing a 25-year period to document the long-term molecular evolution of HBV. The rate, nature, and distribution of mutations that emerged over 25 years were determined by phylogenetic and linear regression analysis of full-length HBV genome sequences. Nucleotide hypervariability was observed within the polymerase and pre-S/S overlap region and within the core gene. The calculated mean number of nucleotide substitutions/site/year (7.9 × 10−5) was slightly higher than published estimates (1.5 × 10−5 to 5 × 10−5). Nucleotide changes in the quasispecies population did not significantly alter the molecular evolutionary rate, based on linear regression analysis of evolutionary distances among serial clone pre-S region sequences. Therefore, the directly amplified or dominant sequence was sufficient to estimate the putative molecular evolutionary rate for these long-term serial samples. On average, the ratio of synonymous (dS) to nonsynonymous (dN) substitutions was highest for the polymerase-coding region and lowest for the core-coding region. The low dS/dN ratios observed within the core suggest that selection occurs within this gene region, possibly as an immune evasion strategy. The results of this study suggest that HBV sequence divergence may occur more rapidly than previously estimated, in a host immune phase-dependent manner.
Estimation of water extraction fractions in rat brain using magnetic resonance measurement of perfusion with arterial spin labeling

The model used for calculating perfusion by MRI techniques that use endogenous water as a tracer assumes that arterial water is a freely diffusible tracer. Evidence shows that this assumption is not valid in the brain at high blood flow rates, at which movement of water into and out of the microvasculature becomes limited by diffusion across the blood‐brain barrier. In this work, the arterial spin‐labeling technique is used to show that fraction of arterial water that is dependent on blood flow rate remains in the vasculature and does not exchange with brain tissue water. By using perfusion measurements without and with magnetization transfer (MT) effects, one can distinguish arterial label that exchanges into tissue because blood has much smaller MT than brain tissue. Using this technique, the extraction fraction for water is measured in the rat brain at various cerebral blood flow rates. At high flow rates (‐5 ml/g/min), the extraction fraction for water is found to be about 45% in rat brain. Disruption of the blood‐brain barrier with D‐mannitol caused an increase in the extraction fraction for water. It was possible to form an image related to the extraction fraction for water. The ability to estimate the amount of vascular water exchanging with tissue water by MRI may represent a noninvasive approach to detect the integrity of the blood‐brain barrier.
Lateral Pupil Alignment Tolerance in Peripheral Refractometry

Purpose. To investigate the tolerance to lateral pupil misalignment in peripheral refraction compared with central refraction. Methods. A Shin-Nippon NVision-K5001 open-view auto-refractor was used to measure central and peripheral refraction (30° temporal and 30° nasal visual field) of the right eyes of 10 emmetropic and 10 myopic participants. At each of the three fixation angles, five readings were recorded for each of the following alignment positions relative to pupil center: centrally aligned, 1 and 2 mm temporally aligned, and 1 and 2 mm nasally aligned. Results. For central fixation, increasing dealignment from pupil center produced a quadratic decrease (r ≥0.98, p < 0.04) in the refractive power vectors M and J180 which, when interpolated, reached clinical significance (i.e., ≥0.25 diopter for M and ≥0.125 diopter for J180 and J45) for an alignment error of 0.79 mm or greater. M and J180 as measured in the 30° temporal and 30° nasal visual field led to a significant linear correlation (r ≥0.94, p < 0.02) as pupil dealignment gradually changed from temporal to nasal. As determined from regression analysis, a pupil alignment error of 0.20 mm or greater would introduce errors in M and J180 that are clinically significant. Conclusions. Tolerance to lateral pupil alignment error decreases strongly in the periphery compared with the greater tolerance in central refraction. Thus, precise alignment of the entrance pupil with the instrument axis is critical for accurate and reliable peripheral refraction.