Miracle-dz/UniFAR-FTUs huggingface dataset:
History of the ribosome and the origin of translation

Significance The ribosome, in analogy with a tree, contains a record of its history, spanning 4 billion years of life on earth. The information contained within ribosomes connects us to the prehistory of biology. Details of ribosomal RNA variation, observed by comparing three-dimensional structures of ribosomes across the tree of life, form the basis of our molecular-level model of the origins and evolution of the translational system. We infer many steps in the evolution of translation, mapping out acquisition of structure and function, revealing much about how modern biology originated from ancestral chemical systems. We present a molecular-level model for the origin and evolution of the translation system, using a 3D comparative method. In this model, the ribosome evolved by accretion, recursively adding expansion segments, iteratively growing, subsuming, and freezing the rRNA. Functions of expansion segments in the ancestral ribosome are assigned by correspondence with their functions in the extant ribosome. The model explains the evolution of the large ribosomal subunit, the small ribosomal subunit, tRNA, and mRNA. Prokaryotic ribosomes evolved in six phases, sequentially acquiring capabilities for RNA folding, catalysis, subunit association, correlated evolution, decoding, energy-driven translocation, and surface proteinization. Two additional phases exclusive to eukaryotes led to tentacle-like rRNA expansions. In this model, ribosomal proteinization was a driving force for the broad adoption of proteins in other biological processes. The exit tunnel was clearly a central theme of all phases of ribosomal evolution and was continuously extended and rigidified. In the primitive noncoding ribosome, proto-mRNA and the small ribosomal subunit acted as cofactors, positioning the activated ends of tRNAs within the peptidyl transferase center. This association linked the evolution of the large and small ribosomal subunits, proto-mRNA, and tRNA.
Case‐control study of proximal and distal colon cancer and diet in Wisconsin

The relationship between diet and subsite‐specific colon cancer was investigated using dietary histories obtained from a statewide, population‐based sample of 152 proximal colon cancer patients, 201 distal colon cancer patients and 618 general population controls. The results do not support hypotheses that (1) dietary fat and cholesterol are more strongly related to proximal colon cancer and (2) vegetables and other dietary sources of fiber are more strongly associated with distal colon cancer. Vegetable consumption over lifetime was consistently protective for both proximal and distal colon cancer. Odds ratios and 95% confidence intervals for the most significant dietary factors (based on high vs. low consumption) for proximal colon cancer were: salad, 0.29 (0.17, 0.48); miscellaneous vegtables, 0.58 (0.35, 0.97); cruciferous vegetables, 0.59 (0.35, 0.97); processed lunchmeat, 2.04 (1.31, 3.17); panfried foods, 1.79 (1.15, 2.80); eggs, 1.75 (1.02, 2.99) and for distal colon cancer they were: salad, 0.43 (0.28, 0.67); cruciferous vegetables, 0.44 (0.28, 0.71); cheese, 0.62 (0.40, 0.96); processed lunchmeat, 1.79 (1.17, 2.73); pan‐fried foods, 1.55 (1.03, 1.27). The results support recommendations that the “prudent diet” (low‐fat, high‐vegetable) may reduce colon cancer risk.
Cost-effectiveness analysis of targeted and sequential screening strategies for latent tuberculosis.

SETTING No cost-effectiveness studies of testing for latent tuberculosis infection have incorporated both targeted testing and the use of interferon-gamma release assays (IGRAs) in heterogeneous populations. OBJECTIVE To examine the cost-effectiveness of universal vs. targeted and sequential testing strategies and the use of tuberculin skin testing (TST) vs. IGRAs. DESIGN Using a decision-analytic model, incremental cost-effectiveness ratios were calculated in 2009 among nine potential strategies for screening recruits. A societal perspective was taken over a 20-year analytic horizon, discounting future costs at 3% annually. Sensitivity analyses were conducted to determine how changes in assumptions affected the estimates. RESULTS Targeted strategies cost over US$250 000 per case prevented, whereas universal testing strategies cost over US$700 000 per incremental case prevented in base case and most sensitivity analyses. CONCLUSION Targeted testing offered the best value in this population, although it was still relatively expensive compared to no testing. Sequential testing with both TST and IGRAs provided a poor incremental value compared to targeted and universal testing strategies. Targeted testing using TST was slightly more cost-effective than targeted testing using either QuantiFERON®-TB Gold In-Tube or T-SPOT®. TB, but these estimates were very sensitive to changes in model assumptions.
Carotid endarterectomy with primary closure: analysis of outcomes and review of the literature.

BACKGROUND Despite abundant published support of patch angioplasty during carotid endarterectomy (CEA), primary closure is still widely used. The reasons underlying the persistence of primary closure are not quite evident in the literature. OBJECTIVE To present our experience with primary closure in CEA, and provide a rationale for its persistent wide use. METHODS Medical records of all patients undergoing CEA by the senior author (R.F.) were retrospectively reviewed. Follow-up was supplemented with a telephone interview and completion of a structured questionnaire. A review of the current literature was performed. RESULTS From 1998 to 2010, the senior author performed 111 CEAs. Average cross-clamp time was 33 ± 11 minutes. Postoperative complications included 1 non-ST-elevation myocardial infarction and 2 strokes. No deaths, cranial-nerve deficits, or acute reocclusions were observed. After a mean follow-up of 64.6 months (7170.6 case-months), there were 3 contralateral strokes and 7 deaths. There were no ipsilateral strokes or restenoses >50%. Follow-up medication compliance was 94.6% for antiplatelet agents and 91.9% for statins. The outcomes of the current study were comparable to those of the available trials comparing patch angioplasty with primary closure. A careful evaluation of the literature revealed a number of reasons potentially explaining the persistent use of patch angioplasty. CONCLUSION In conjunction with contemporary medical management, primary closure during CEA may yield results comparable or superior to patch angioplasty. Advantages of primary closure include shorter cross-clamp times and elimination of graft-specific complications.
Electron microscopic cytochemical localization of Ca‐ATPase in the rod outer segments of the toad Bufo marinus

Transmission electron microscopy and ultracytochemistry were employed in an attempt to localize the enzyme calcium adenosine triphosphatase (Ca‐ATPase) in the rod outer segments (ROS) of the toad retina. Utilizing a one‐step incubation procedure, Ca‐ATPase was identified as an electron‐dense precipitate in the intradiskal spaces of the rod disks (vesicles) of the ROS. Analytical microscopy identified the reaction product as lead phosphate. The formation of the reaction product was dependent on the presence of ATP (the substrate) and calcium ions. However, calcium ions could be substituted for by magnesium ions. In addition, the reaction was vanadate sensitive. The latter is known to inhibit Ca‐ATPase activity. Such data appear to indicate the presence of a Ca‐Mg‐ATPase in association with the rod disks. Since cyclic guanosine monophosphate (cyclic GMP), rather than calcium ions, is currently believed to be the primary intracellular messenger associated with phototransduction, the presence of an ROS Ca‐ATPase may indicate other functions for this cation in the physiology and biochemistry of the visual process. Ca‐ATPase might play a role in directional calcium fluxes between intracellular compartments.
The Arf‐inducing transcription factor Dmp1 encodes a transcriptional activator of amphiregulin, thrombospondin‐1, JunB and Egr1

Dmp1 (Dmtf1) encodes a Myb‐like transcription factor implicated in tumor suppression through direct activation of the Arf‐p53 pathway. The human DMP1 gene is frequently deleted in non‐small cell lung cancers, especially those that retain wild‐type INK4a/ARF and/or p53. To identify novel genes that are regulated by Dmp1, transcriptional profiles of lung tissue from Dmp1‐null and wild‐type mice were generated using the GeneChip Microarray. Comparative analysis of gene expression changes between the two groups resulted in identification of numerous genes that may be regulated by Dmp1. Notably, amphiregulin (Areg), thrombospondin‐1 (Tsp‐1), JunB, Egr1, adrenomedullin (Adm), Bcl‐3 and methyl‐CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1‐null mice while Gas1 and Ect2 genes were upregulated. These target genes were chosen for further analyses since they are involved in cell proliferation, transcription, angiogenesis/metastasis, apoptosis, or DNA methylation, and thus could account for the tumor suppressor phenotype of Dmp1. Dmp1 directly bound to the genomic loci of Areg, Tsp‐1, JunB and Egr1. Significant upregulation or downregulation of the novel Dmp1 target genes was observed upon transient expression of Dmp1 in alveolar epithelial cells, an effect which was nullified by the inhibition of de novo mRNA synthesis. Interestingly, these genes and their protein products were significantly downregulated or upregulated in the lungs from Dmp1‐heterozygous mice as well. Identification of novel Dmp1 target genes not only provides insights into the effects of Dmp1 on global gene expression, but also sheds light on the mechanism of haploid insufficiency of Dmp1 in tumor suppression.
Perfil Socioeconômico dos Consumidores de Restaurantes em Relação À Valorização de Produtos Orgânicos: Uma Análise Comparativa

This article aims to analyze comparatively the socioeconomic profile of consumers who value and those who do not value organic products in restaurants. To achieve this purpose, 392 customers were interviewed in two restaurants from a large supermarket network by means of a structured questionnaire. Regarding the cross-analysis between the profile of consumers and the enhancement of organic products, the research has found out that: (a) women value most organic products than men; (b) the higher the educational level of analyzed individuals, the greater the appreciation shown by them on the subject; (c) consumers with an income above three minimum wages value more organic products than persons with a lower income; however, from three minimum wages, the percentage of the valuation remains; and (d) consumers over 40 years of age value more organic products than younger consumers. It is emphasized that the findings presented in this article contribute to the formation of the body of scientific knowledge about organic consumers, that does not exclude, however, their need to be considered with caution, considering that they do not allow inferences that go beyond the investigated sample. As an empirical contribution, so, the broader understanding of these consumers, so as to better serve them, becomes an important aspect so shops can succeed.
Echinocandin Resistance in Candida Species: Mechanisms of Reduced Susceptibility and Therapeutic Approaches

OBJECTIVE: To summarize published data regarding mechanisms of reduced echinocandin susceptibility in Candida spp. , the impact of echinocandin resistance on the fitness and virulence of Candida isolates, and current and future treatment approaches. DATA SOURCES: A search of MEDLINE databases (1966-September 2011) was conducted. STUDY SELECTION AND DATA EXTRACTION: Databases were searched using the terms echinocandin, resistance, and Candida. Citations from publications were reviewed for additional references. DATA SYNTHESIS: Echinocandins have in vitro activity against most Candida spp. and are first-line agents in the treatment of candidemia. However, case reports describing echinocandin treatment failure due to resistant isolates have been published. Reduced echinocandin susceptibility has been shown to occur via 3 main mechanisms: (1) adaptive stress responses, which result in elevated cell wall chitin content and paradoxical growth in vitro at supra minimum inhibitory concentrations (MICs); (2) acquired FKS mutations, which confer reduced glucan synthase sensitivity, elevated MICs, and are associated with clinical failure; and (3) intrinsic FKS mutations, which are naturally occurring mutations in C. parapsilosis and C. guilliermondii, which confer elevated MIC levels but a lower level of reduced glucan synthase sensitivity compared with acquired FKS mutations. Some FKS mutants have been shown to have significantly reduced fitness and virulence versus wild type isolates and may contribute to the low incidence of echinocandin resistance reported in large surveillance studies. Treatment strategies evaluated for FKS mutants include echinocandin dose escalation and combination with agents such as calcineurin inhibitors, HSP90 inhibitors, and chitin synthase inhibitors. CONCLUSIONS: While the incidence of echinocandin resistance in Candida spp. is low, it can present a significant therapeutic challenge, especially in multidrug-resistant Candida isolates. Dose escalation is unlikely to be effective in treating FKS mutant isolates, and significant adverse effects limit the clinical use of agents evaluated as combination therapy. Patients with infections failing to respond to echinocandin therapy should undergo susceptibility testing and be treated with an alternative antifungal agent if possible.
Replacing a Dopamine Agonist by the COMT-Inhibitor Tolcapone as an Adjunct to l-dopa in the Treatment of Parkinson's Disease: A Randomized, Multicenter, Open-Label, Parallel-Group Study

Objective:This study investigated the feasibility, safety, and potential benefit in motor symptom control when switching from a dopamine agonist to tolcapone as an adjunctive therapy in patients with Parkinson's disease with a fluctuating response to levodopa (l-dopa). We determined the efficacy of 2 replacement strategies. Methods:In this 10-week, randomized, open-label, stratified, parallel-group trial, 150 patients on a stable regimen of l-dopa/decarboxylase inhibitor in combination with bromocriptine, lisuride, or pergolide were switched to tolcapone. Primary end point was the change in daily "off" time from baseline to the end of week 10 as assessed by patient "on-off" diaries. Patients had their respective dopamine agonist reduced and finally withdrawn either by day 6 (short-term replacement, n = 72) or by day 23 (long-term replacement, n = 78). Results:At week 10, a significant reduction from baseline in daily "off" time (−15.9 ± 19.3%; P < 0.001) and a significant increase of "on" time (14.6 ± 19.8%; P < 0.001) were observed. Other efficacy variables (Unified Parkinson's Disease Rating Scale II, III, and IVb and Investigator's Global Assessment scores) improved significantly after switching to tolcapone. In general, there was no significant difference between the 2 replacement strategies. Treatment was better tolerated after the switch to tolcapone according to the IGA of tolerability. Conclusions:Tolcapone, in principle, seems to be an alternative adjunct for patients, who fail to receive sufficient benefit from a dopamine agonist, for example, in case they do not tolerate an increase in dose or have unacceptable side effects. The switch from a dopamine agonist to tolcapone can be done safely within a few days.
Gene Expression Profile in Temporal Lobe Epilepsy

Epilepsy is one of the most common neurological disorders. Temporal lobe epilepsy (TLE) represents the most frequent epilepsy syndrome in adult patients with resistance to pharmacological treatment. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). The expansion of neurosurgical epilepsy programs has offered the possibility of disposing of clinically well-characterized hippocampal tissue, so that the analysis of molecular mechanisms underlying the structural and functional reorganization occurring in the hippocampus and neighboring areas in TLE patients can be done on a large scale. The recent development of molecular biological technologies permits the analysis of changes in the expression of a large number of genes. This has opened new perspectives for epilepsy research. However, the hippocampal specimens obtained from patients with TLE most often represent an advanced stage of the pathology. For this reason, animal models that reproduce the clinical and histopathological features of TLE are helpful in detecting the early development of the pathological cascade leading to TLE with HS. An overview of recent data of gene expression profiles in human and experimental TLE is presented along with a discussion of the relevance of functional genomics, to develop new hypotheses and to detect likely candidate genes involved in epileptogenesis, as well as possible target molecules for new therapeutic approaches. NEUROSCIENTIST 13(2):100—108, 2007.
5S rRNA fingerprints of marine bacteria, halophilic archaea and natural prokaryotic assemblages along a salinity gradient.

Natural prokaryotic assemblages from two multi-pond solar salterns and pure cultures of both marine bacteria and halophilic archaea were analyzed and compared by electrophoretic analysis of 5S rRNAs. A salinity gradient from seawater (3.7%) to NaCl precipitation (37%) was studied. The culture-independent, PCR-free, fingerprinting analysis covered two objectives: (i) to compare natural assemblages among them and with results previously obtained through a PCR-dependent approach and (ii) to estimate the in situ relevance of those prokaryotic groups obtained with classical culture methodologies. Natural assemblages were analyzed through cluster analysis of quantitative 5S rRNA band patterns. The resulting groups were in accordance with environmental parameters (i.e., NaCl concentration) and with the clustering obtained after a PCR-dependent approach, showing the formation of three salinity-based groups of samples (<10%, 10-25% and >25% salinity). Similarities between the laboratory strains tested and dominant community members were studied by comparing 5S rRNA band patterns. The lack of match obtained after cluster analysis indicated that the prokaryotic populations relevant in the ponds below 25% salinity were neither Flavobacteria nor haloarchaeal strains belonging to the genera Halococcus, Haloarcula and Halobacterium. Members of Proteobacteria and Gram-positive bacteria were found to match bands in these samples. The 5S rRNA fingerprint from the dominant community members in the ponds above 30% salinity did not fit any of the cultured halophilic archaea studied, in agreement with earlier PCR results. This is consistent with a greater bias introduced by culture-dependent methods than by those based on PCR, especially for archaeal populations.
Effect of patients' risks and preferences on health gains with plasma glucose level lowering in type 2 diabetes mellitus.

IMPORTANCE Type 2 diabetes mellitus is common, and treatment to correct blood glucose levels is standard. However, treatment burden starts years before treatment benefits accrue. Because guidelines often ignore treatment burden, many patients with diabetes may be overtreated. OBJECTIVE To examine how treatment burden affects the benefits of intensive vs moderate glycemic control in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS We estimated the effects of hemoglobin A1c (HbA1c) reduction on diabetes outcomes and overall quality-adjusted life years (QALYs) using a Markov simulation model. Model probabilities were based on estimates from randomized trials and observational studies. Simulated patients were based on adult patients with type 2 diabetes drawn from the National Health and Nutrition Examination Study. INTERVENTIONS Glucose lowering with oral agents or insulin in type 2 diabetes. MAIN OUTCOMES AND MEASURES Main outcomes were QALYs and reduction in risk of microvascular and cardiovascular diabetes complications. RESULTS Assuming a low treatment burden (0.001, or 0.4 lost days per year), treatment that lowered HbA1c level by 1 percentage point provided benefits ranging from 0.77 to 0.91 QALYs for simulated patients who received a diagnosis at age 45 years to 0.08 to 0.10 QALYs for those who received a diagnosis at age 75 years. An increase in treatment burden (0.01, or 3.7 days lost per year) resulted in HbA1c level lowering being associated with more harm than benefit in those aged 75 years. Across all ages, patients who viewed treatment as more burdensome (0.025-0.05 disutility) experienced a net loss in QALYs from treatments to lower HbA1c level. CONCLUSIONS AND RELEVANCE Improving glycemic control can provide substantial benefits, especially for younger patients; however, for most patients older than 50 years with an HbA1c level less than 9% receiving metformin therapy, additional glycemic treatment usually offers at most modest benefits. Furthermore, the magnitude of benefit is sensitive to patients' views of the treatment burden, and even small treatment adverse effects result in net harm in older patients. The current approach of broadly advocating intensive glycemic control should be reconsidered; instead, treating patients with HbA1c levels less than 9% should be individualized on the basis of estimates of benefit weighed against the patient's views of the burdens of treatment.
Microbial diversity in soils of agricultural landscapes and its relation to ecosystem function

The taxonomic and functional diversity of microbes in soil is stunning. Although they are largely invisible to the naked eye, microbes are pervasive in nature and have a profound impact on Earth’s habitability. Like many other terrestrial environments, the top layer of soil at the Kellogg Biological Station Long-Term Ecological Research site (KBS LTER) typically contains 1 × 10 microbes per gram of dry soil, representing between 10,000 and a million species (Gans et al. 2005). Extrapolating the estimated number of microbes in individual soil samples to a global scale yields an estimate of an incredible 26 × 10 microbes in terrestrial habitats (Whitman et al. 1998). Combined with estimates of microbial abundance in aquatic and subsurface environments, Whitman and colleagues (1998) estimated that microbes contain at least half of the amount of carbon (C) stored in plants and 10 times more nitrogen (N) and phosphorus (P). The cycling of C, N, P, and other less abundant elements that pass through soil microbial communities influences environments as small as soil aggregates and as far-reaching as global climate. Here, we focus on the composition and function of microbes that drive the cycling of C and N in soils and discuss the ecological significance of their diversity and physiologies within, across, and beyond agricultural landscapes. Compounds containing C and N are major determinants of both crop productivity and climate change, so understanding what controls their transformations will be important for developing agricultural strategies that balance crop yield and ecosystem services against environmental harm. Our emphasis is on discoveries made in the past two decades at KBS LTER, where experiments have maintained different management practices for >20 years and aspects of C and N cycling are well documented (Robertson and Hamilton Schmidt, T. M. and C. Waldron. 2015. Microbial diversity in soils of agricultural landscapes and its relation to ecosystem function. Pages 135-157 in S. K. Hamilton, J. E. Doll, and G. P. Robertson, editors. The Ecology of Agricultural Landscapes: Long-Term Research on the Path to Sustainability. Oxford University Press, New York, New York, USA.