Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcription Initiation by Mix and Match Elements: Flexibility for Polymerase Binding to Bacterial Promoters

Bacterial RNA polymerase is composed of a core of subunits (β, β′, α1, α2, ω), which have RNA synthesizing activity, and a specificity factor (σ), which identifies the start of transcription by recognizing and binding to sequence elements within promoter DNA. Four core promoter consensus sequences, the −10 element, the extended −10 (TGn) element, the −35 element, and the UP elements, have been known for many years; the importance of a nontemplate G at position −5 has been recognized more recently. However, the functions of these elements are not the same. The AT-rich UP elements, the −35 elements (−35TTGACA−30), and the extended −10 (−15TGn−13) are recognized as double-stranded binding elements, whereas the −5 nontemplate G is recognized in the context of single-stranded DNA at the transcription bubble. Furthermore, the −10 element (−12TATAAT−7) is recognized as both double-stranded DNA for the T:A bp at position −12 and as nontemplate, single-stranded DNA from positions −11 to −7. The single-stranded sequences at positions −11 to −7 as well as the −5 contribute to later steps in transcription initiation that involve isomerization of polymerase and separation of the promoter DNA around the transcription start site. Recent work has demonstrated that the double-stranded elements may be used in various combinations to yield an effective promoter. Thus, while some minimal number of contacts is required for promoter function, polymerase allows the elements to be mixed and matched. Interestingly, which particular elements are used does not appear to fundamentally alter the transcription bubble generated in the stable complex. In this review, we discuss the multiple steps involved in forming a transcriptionally competent polymerase/promoter complex, and we examine what is known about polymerase recognition of core promoter elements. We suggest that considering promoter elements according to their involvement in early (polymerase binding) or later (polymerase isomerization) steps in transcription initiation rather than simply from their match to conventional promoter consensus sequences is a more instructive form of promoter classification.
Physical, psychological and chemical triggers of acute cardiovascular events: preventive strategies.

In addition to the impact of long-term stressors such as sedentary lifestyle and long-term exposure to high levels of air pollution, many studies have shown that there is an increased risk of acute cardiovascular events immediately after behavioral, psychosocial, and environmental triggers.1–8 After the landmark study documenting the increased rates of myocardial infarction (MI) related to the 1981 earthquake in Athens9 and the description of the circadian variation in the incidence of MI by Muller et al,10 various studies documented the frequency of potential triggers in the period immediately preceding MI onset. Although the observational studies examining physical, psychological, and chemical triggers of acute cardiovascular events are not without limitations, studies continue to show that short-term exposures appear to play a role in the occurrence of cardiovascular events. These triggers have been discussed in previous reviews,1–8 with a general consensus that different preventive strategies may be appropriate for particular triggers. The purpose of this review is to bring together the evidence of the association between several triggers and cardiovascular outcomes and to discuss the common underlying pathophysiology of these triggers. Rather than leading to slowly progressive atherosclerosis, triggers represent the final step in the pathophysiological process leading to cardiovascular outcomes among susceptible individuals, such as those with vulnerable atherosclerotic plaque, chronic atherosclerotic disease, disorders of the cardiac conduction system, and microvascular disease. In the presence of a vulnerable atherosclerotic plaque, chemical, physical, and psychological stressors may trigger transient vasoconstrictive and prothrombotic effects that ultimately cause plaque disruption and thrombosis. Even in the absence of an occlusive thrombus, triggers may lower the threshold for cardiac electric instability and increase cardiac sympathetic activation via centrally mediated release of catecholamines, thereby evoking primary ventricular fibrillation and sudden cardiac death.11 Figure 1 depicts several potential …
Role of Cell Surface Metalloprotease Mt1-Mmp in Epithelial Cell Migration over Laminin-5

Laminin-5 (Ln-5) is an extracellular matrix substrate for cell adhesion and migration, which is found in many epithelial basement membranes. Mechanisms eliciting migration on Ln-5 need to be elucidated because of their relevance to tissue remodeling and cancer metastasis. We showed that exogenous addition of activated matrix metalloprotease (MMP) 2 stimulates migration onto Ln-5 in breast epithelial cells via cleavage of the γ2 subunit. To investigate the biological scope of this proteolytic mechanism, we tested a panel of cells, including colon and breast carcinomas, hepatomas, and immortalized hepatocytes, selected because they migrated or scattered constitutively in the presence of Ln-5. We found that constitutive migration was inhibited by BB94 or TIMPs, known inhibitors of MMPs. Limited profiling by gelatin zymography and Western blotting indicated that the ability to constitutively migrate on Ln-5 correlated with expression of plasma membrane bound MT1-MMP metalloprotease, rather than secretion of MMP2, since MMP2 was not produced by three cell lines (one breast and two colon carcinomas) that constitutively migrated on Ln-5. Moreover, migration on Ln-5 was reduced by MT1-MMP antisense oligonucleotides both in MMP2+ and MMP2− cell lines. MT1-MMP directly cleaved Ln-5, with a pattern similar to that of MMP2. The hemopexin-like domain of MMP2, which interferes with MMP2 activation, reduced Ln-5 migration in MT1-MMP+, MMP2+ cells, but not in MT1-MMP+, MMP2− cells. These results suggest a model whereby expression of MT1-MMP is the primary trigger for migration over Ln-5, whereas MMP2, which is activated by MT1-MMP, may play an ancillary role, perhaps by amplifying the MT1-MMP effects. Codistribution of MT1-MMP with Ln-5 in colon and breast cancer tissue specimens suggested a role for this mechanism in invasion. Thus, Ln-5 cleavage by MMPs may be a widespread mechanism that triggers migration in cells contacting epithelial basement membranes.
A Practical Model for Organic Richness from Porosity and Resistivity Logs

A practical method, the delta log R technique, for identifying and calculating total organic carbon in organic-rich rocks has been developed using well logs. The method employs the overlaying of a properly scaled porosity log (generally the sonic transit time curve) on a resistivity curve (preferably from a deep-reading tool). In water-saturated, organic-lean rocks, the two curves parallel each other and can be overlain, since both curves respond to variations in formation porosity; however, in either hydrocarbon reservoir rocks or organic-rich non-reservoir rocks, a separation between the curves occurs. Using the gamma-ray curve, reservoir intervals can be identified and eliminated from the analysis. The separation in organic-rich intervals results from two effects: the orosity curve responds to the presence of low-density, low-velocity kerogen, and the resistivity curve responds to the formation fluid. In an immature organic-rich rock, where no hydrocarbons have been generated, the observed curve separation is due solely to the porosity curve response. In mature source rocks, in addition to the porosity curve response, the resistivity increases because of the presence of generated hydrocarbons. The magnitude of the curve separation in non-reservoirs is calibrated to total organic carbon and maturity, and allows for depth profiling of organic richness in the absence of sample data. This method allows organic richness to be accurately assessed in a wide variety of lithologies and maturities using common well logs.
Water‐Quality Assessment of the Lower Grand River Basin, Missouri and Iowa, USA, in Support of Integrated Conservation Practices

The effectiveness of agricultural conservation programmes to adequately reduce nutrient exports to receiving streams and to help limit downstream hypoxia issues remains a concern. Quantifying programme success can be difficult given that short‐term basin changes may be masked by long‐term water‐quality shifts. We evaluated nutrient export at stream sites in the 44 months that followed a period of increased, integrated conservation implementation within the Lower Grand River Basin. These short‐term responses were then compared with export that occurred in the main stem and adjacent rivers in northern Missouri over a 22‐year period to better contextualize any recent changes. Results indicate that short‐term (October 2010 through May 2014) total nitrogen (TN) concentrations in the Grand River were 20% less than the long‐term average, and total phosphorus (TP) concentrations were 23% less. Nutrient reductions in the short term were primarily the result of the less‐than‐average precipitation and, consequently, streamflow that was 36% below normal. Therefore, nutrient concentrations measured in tributary streams were likely less than normal during the implementation period. Northern Missouri streamflow‐normalized TN concentrations remained relatively flat or declined over the period 1991 through 2013 likely because available sources of nitrogen, determined as the sum of commercial fertilizers, available animal manures and atmospheric inputs, were typically less than crop requirement for much of that time frame. Conversely, flow‐normalized stream TP concentrations increased over the past 22 years in northern Missouri streams, likely in response to many years of phosphorus inputs in excess of crop requirements. Stream nutrient changes were most pronounced during periods that coincided with the major tillage, planting and growth phases of row crops and increased streamflow. Nutrient reduction strategies targeted at the period February through June would likely have the greatest impact on reducing nutrient export from the basin. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Nitrogen and Water Interactions in Trickle‐Irrigated Watermelon

Rising water costs and concern for groundwater contamination by NO 3 and other agricultural chemicals are forcing growers in arid regions to improve irrigation and N fertilization efficiency. Applying N and water through a subsurface drip irigation system in conjunction with in-season monitoring techniques for assessing crop water and N status has the potential to greatly improve water and N use efficiency. The objectives of this research were to: (i) investigate the interactive effects of water and N applied through a subsurface trickle irrigation system on watermelon [Citrullus lanatus (Thumb.) Matsum and Nakai var. lanatus] fruit yield and on the potential for leaching losses of NO 3 , and (ii) determine the optimum range of soil water tension for subsurface trickle-irrigated watermelon. Field experiments were conducted during 1990 and 1991 on a reclaimed Casa Grande soil (fine-loamy, mixed, hyperthermic Typic Natrargid) in southern Arizona. Levels of target soil water tensions and fertilizer N were arranged in a factorial design to determine fruit yield response surfaces. Tensiometers at 0.3- and 0.6-m depth were used to monitor soil water tension throughout the growing season. Marketable watermelon yield showed a pronounced positive water × N interaction in both years of the study. Predicted marketable yields were 90 Mg ha -1 when mean soil water tension was 6 kPa and applied N was between 200 and 270 kg ha -1 in 1990 and a predicted yield minimum of 102 Mg ha -1 at 7.2 kPa and 336 kg N ha -1 in 1991. Scheduling of irrigations using feedback from tensiometers proved very useful in providing optimum amounts of water while avoiding conditions that favor N loss through leaching or denitrification
Erv41p and Erv46p: New Components of Copii Vesicles Involved in Transport between the Er and Golgi Complex

Proteins contained on purified COPII vesi-cles were analyzed by matrix-assisted laser desorption ionization mass spectrometry combined with database searching. We identified four known vesicle proteins and Emp47p) that had not been localized to ER vesicles. Using antibodies, we demonstrate that these proteins are selectively and efficiently packaged into COPII vesicles. Three of the newly identified vesicle proteins (Erv29p, Erv41p, and Erv46p) represent uncharacterized integral membrane proteins that are conserved across species. Erv41p and Erv46p were further characterized. These proteins co-localized to ER and Golgi membranes and exist in a detergent-soluble complex that was isolated by immu-noprecipitation. Yeast strains lacking Erv41p and/or Erv46p are viable but display cold sensitivity. The expression levels of Erv41p and Erv46p are interdependent such that Erv46p was reduced in an erv41 ⌬ strain, and Erv41p was not detected in an erv46 ⌬ strain. When the erv41 ⌬ or ev46 ⌬ alleles were combined with other mutations in the early secretory pathway, altered growth phenotypes were observed in some of the double mutant strains. A cell-free assay that reproduces transport between the ER and Golgi indicates that deletion of the Erv41p–Erv46p complex influences the membrane fusion stage of transport.
ADAMs 10 and 17 Represent Differentially Regulated Components of a General Shedding Machinery for Membrane Proteins Such as Transforming Growth Factor (cid:1) , L-Selectin, and Tumor Necrosis Factor (cid:1)

Protein ectodomain shedding is a critical regulator of many membrane proteins, including epidermal growth factor receptor-ligands and tumor necrosis factor (TNF)- (cid:1) , providing a strong incentive to deﬁne the responsible sheddases. Previous studies identiﬁed ADAM17 as principal sheddase for transforming growth factor (TGF)- (cid:1) and heparin-binding epidermal growth factor, but Ca (cid:2)(cid:2) inﬂux activated an additional sheddase for these epidermal growth factor receptor ligands in Adam17 (cid:3) / (cid:3) cells. Here, we show that Ca (cid:2)(cid:2) inﬂux and stimulation of the P2X7R signaling pathway activate ADAM10 as sheddase of many ADAM17 substrates in Adam17 (cid:3) / (cid:3) ﬁbroblasts and primary B cells. Importantly, although ADAM10 can shed all substrates of ADAM17 tested here in Adam17 (cid:3) / (cid:3) cells, acute treatment of wild-type cells with a highly selective ADAM17 inhibitor (SP26) showed that ADAM17 is nevertheless the principal sheddase when both ADAMs 10 and 17 are present. However, chronic treatment of wild-type cells with SP26 promoted processing of ADAM17 substrates by ADAM10, thus generating conditions such as in Adam17 (cid:3) / (cid:3) cells. These results have general implications for understanding the substrate selectivity of two major cellular sheddases, ADAMs 10 and 17. but because its expression level varied greatly from one mouse to another, data were further normalized to the untreated control to allow comparisons of individual experiments.
Interaction of smoking and social status on the risk of respiratory outcomes in a Swedish adult population: A Nordic Epilung study.

BACKGROUND Evidence abounds on the independent roles of social class and smoking in relation to obstructive airway diseases, but data are sparse on the impact of their interaction. We evaluated whether and to what extent social class and smoking interact in relation to risk of respiratory diseases in adults. METHODS Data from the population-based studies, West Sweden Asthma Study (WSAS, n = 23,753) and Obstructive Lung Disease in Northern Sweden studies (OLIN, n = 6519), were used, constituting randomly selected adults aged 20-75 years. Bayesian network analysis was used to estimate the probability for the interaction between smoking and socioeconomic status in relation to respiratory outcomes. RESULTS Occupational and educational SES modified the association between smoking and the probability of allergic and non-allergic asthma. Former smokers who were at intermediate non manual employees and manual workers in service had higher probability of allergic asthma compared to professionals and executives. Furthermore, former smokers with primary education had higher probability of non-allergic asthma than those with secondary and tertiary education. Similarly, former smokers among professionals and executives had higher probability of non-allergic asthma than manual and home workers and primary educated. Likewise, allergic asthma due to former smoking was higher among highly educated compared to low educated. CONCLUSIONS Beyond their independent roles, socioeconomic status and smoking interact in defining the risk of respiratory diseases. Clearer understanding of this interaction can help to identify population subgroups at most need of public health interventions.
Apopain/CPP32 Cleaves Proteins That Are Essential for Cellular Repair: A Fundamental Principle of Apoptotic Death By Livia Casciola-Rosen,** DonaldW. Nicholson,II Tae Chongfl

Summary Proteolysis mediated by the interleukin 1[3-converting enzyme (ICE) homologues is an important mechanism of the apoptotic process. The ICE homologue apopain/CPP-32/Yama (subsequently referred to as apopain) cleaves poly(ADP-ribose)polymerase (PAR.P) early during apoptosis. Additional apoptosis-specific protein cleavages have been observed in which the direct involvement of ICE-like proteases has been postulated. These substrates include the 70-kD protein component of the Ul-ribonucleoprotein (U1-70kD), and the catalytic subunit of the DNAdependent protein kinase (DNA-PKcs). The present studies demonstrate that U1-70kD and DNA-PK~ are excellent substrates for apopain, with cleavage occurring at sites that are highly similar to the cleavage site within PAR.P. The fragments generated from isolated protein substrates by apopain are identical to those observed in intact apoptotic cells, in apoptotic cell extracts, and in normal cell extracts to which apopain has been added. Like PARP, cleavage of these substrates in apoptotic cell extracts is abolished by nanomolar concentrations of AcDEVD-CHO and micromolar amounts of Ac-YVAD-CHO, confirming the involvement of apopain or an apopain-like activity. We propose that a central function of apopain or similar homologues in apoptosis is the cleavage of nuclear repair proteins, thereby abolishing their critical homeostatic functions.
Pancreatic Resection Guided by Preoperative Intraductal Ultrasonography for Intraductal Papillary Mucinous Neoplasm

pISSN 2465-7786•eISSN 2465-7794 www.clinicalultrasound. org Received : 2017. 3. 23 Revised : 2017. 4. 20 Accepted : 2017. 5. 4 Address for Correspondence: Young Koog Cheon, M.D., Ph.D. Division of Gastroenterology, Department of Internal Medicine, Konkuk University School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea Tel: +82-2-2030-8109, Fax: +82-2-2030-5029 E-mail: yksky001@hanmail.net Background/Aims: Successful treatment requires reliable preoperative assessment of the highly variable extension of intraductal papillary mucinous neoplasm (IPMN). We aimed to determine the role of intraductal ultrasonography (IDUS) in predicting the extension of IPMN, and in selecting the method of pancreatic resection and the long-term outcome after surgery. Methods: Randomized prospective study. Forty consecutive patients who underwent IPMN resection were included in the study. Patients were randomly assigned to an IDUS group or control group in which IDUS was not performed. Results: Preoperative assessment by IDUS had an 85% (17/20) diagnostic accuracy for tumor extension of IPMN compared to 50% (10/20) in cases assessed by other imaging methods without IDUS (p = 0.018). In 9 of 15 patients with invasive carcinoma, the tumor was located in the pancreatic head, and 11 had a main duct-type tumor. Recurrent disease was identified in 5 of 15 (33%) patients with invasive IPMN at a mean follow-up of 50 months; of them, 1 underwent preoperative IDUS and 4 were assessed by other imaging methods. None of the 25 patients with noninvasive IPMN had recurrent disease at follow-up. The overall cumulative 3-year survival rate was 79%. Conclusion: Preoperative IDUS was useful in determining the type of surgery and the extent of resection, especially in main-duct IPMN.
Regulatory Cd4 Ϩ T Cells Expressing Endogenous T Cell Receptor Chains Protect Myelin Basic Protein–specific Transgenic Mice from Spontaneous Autoimmune Encephalomyelitis

The development of T cell–mediated autoimmune diseases hinges on the balance between ef-fector and regulatory mechanisms. Using two transgenic mouse lines expressing identical mye-lin basic protein (MBP)–specific T cell receptor (TCR) genes, we have previously shown that mice bearing exclusively MBP-specific T cells (designated T/R Ϫ) spontaneously develop experimental autoimmune encephalomyelitis (EAE), whereas mice bearing MBP-specific T cells as well as other lymphocytes (designated T/R ϩ) did not. Here we demonstrate that T/R Ϫ mice can be protected from EAE by the early transfer of total splenocytes or purified CD4 ϩ T cells from normal donors. Moreover, whereas T/R ϩ mice crossed with B cell–deficient, ␥ր␦ T cell–deficient, or major histocompatibility complex class I–deficient mice did not develop EAE spontaneously, T/R ϩ mice crossed with TCR-␣ and-␤ knockout mice developed EAE with the same incidence and severity as T/R Ϫ mice. In addition, MBP-specific transgenic mice that lack only endogenous TCR-␣ chains developed EAE with high incidence but reduced severity. Surprisingly, two-thirds of MBP-specific transgenic mice lacking only endogenous TCR-␤ chains also developed EAE, suggesting that in T/R ϩ mice, cells with high protective activity escape TCR-␤ chain allelic exclusion. Our study identifies CD4 ϩ T cells bearing endogenous ␣ and ␤ TCR chains as the lymphocytes that prevent spontaneous EAE in T/R ϩ mice. A utoreactive CD4 ϩ T cells are believed to play a major role in chronic inflammatory diseases such as multiple sclerosis, diabetes, and rheumatoid arthritis. However, the mere presence of CD4 ϩ autoreactive T cells is not sufficient for development of autoimmune diseases (1), as a number of investigators have detected self-antigen–specific T cells in normal individuals (2–5). Moreover, the frequency of such self-reactive T cells is often similar between normal individuals and those afflicted with autoimmune diseases. For instance, myelin basic protein (MBP)-reactive 1 T cells constituted 7.18 Ϯ 2.38% of T cell lines derived from patients with multiple sclerosis, and 4.70 Ϯ 1.58% of the T cell lines derived from normal individuals, a difference considered not significant (6). More surprisingly, even in systems with an artificially high frequency of self-reactive CD4 ϩ T cells, such as TCR transgenic mice, only a small proportion of mice develop spontaneous autoimmune diseases under normal, pathogen-free conditions (7, 8). In the latter cases, self-reactive T cells were shown to be generated in large numbers, migrated normally to the peripheral lymphoid organs, and responded well to the self-antigen …
AAIP 2009 Proceedings of the ACM SIGPLAN Workshop on Approaches and Applications of Inductive Programming

It is a well known fact that there is a correspondence between propositions and type, and similarly a correspondence between a proof of a proposition and a program of a type; this is the Curry-Howard correspondence. In this talk I will describe a program, Djinn, which takes a Haskell type and produces a program of that type, using the Curry-Howard correspondence. For the subset of Haskell types that Djinn can handle (no recursive types) it does quite well. For instance, it can derive the code for all the standard monads in Haskell, including continuations and call/cc.