Miracle-dz/UniFAR-FTUs huggingface dataset:
S100–annexin complexes – structural insights

Annexins and S100 proteins represent two large, but distinct, calcium‐binding protein families. Annexins are made up of a highly α‐helical core domain that binds calcium ions, allowing them to interact with phospholipid membranes. Furthermore, some annexins, such as annexins A1 and A2, contain an N‐terminal region that is expelled from the core domain on calcium binding. These events allow for the interaction of the annexin N‐terminus with target proteins, such as S100. In addition, when an S100 protein binds calcium ions, it undergoes a structural reorientation of its helices, exposing a hydrophobic patch capable of interacting with its targets, including the N‐terminal sequences of annexins. Structural studies of the complexes between members of these two families have revealed valuable details regarding the mechanisms of the interactions, including the binding surfaces and conformation of the annexin N‐terminus. However, other S100–annexin interactions, such as those between S100A11 and annexin A6, or between dicalcin and annexins A1, A2 and A5, appear to be more complicated, involving the annexin core region, perhaps in concert with the N‐terminus. The diversity of these interactions indicates that multiple forms of recognition exist between S100 proteins and annexins. S100–annexin interactions have been suggested to play a role in membrane fusion events by the bridging together of two annexin proteins, bound to phospholipid membranes, by an S100 protein. The structures and differential interactions of S100–annexin complexes may indicate that this process has several possible modes of protein–protein recognition.
Laparoscopic enterocystoplasty.

OBJECTIVES To report the initial clinical experience with laparoscopic augmentation enterocystoplasty using the ileum, sigmoid, or right colon. METHODS Three patients with functionally reduced bladder capacities due to neurogenic causes underwent laparoscopic enterocystoplasty: ileocystoplasty (n = 1), sigmoidocystoplasty (n = 1), and cystoplasty with cecum and proximal ascending colon (n = 1). In the last patient, a continent, catheterizable, ileal conduit with an umbilical stoma was also created. In all patients, bowel reanastomosis was performed by exteriorizing the bowel loop outside the abdomen through a 2-cm extension of the umbilical port site. Creation of a large cystotomy, mobilization of the appropriate bowel segment, and the circumferential enterovesical anastomosis were all performed intracorporeally by laparoscopic techniques. RESULTS The operative times were 5.3, 8, and 7 hours. All three laparoscopic enterovesical anastomoses were watertight, without postoperative urinary extravasation. The hospital stay was 7, 5, and 4 days. CONCLUSIONS Laparoscopic enterocystoplasty is feasible, safe, and efficacious and appears to be an attractive alternative to open enterocystoplasty. Various bowel segments can be used as with open surgery, including creation of a continent, catheterizable stoma. Although further technical refinements will undoubtedly occur, even at this early stage, it is clear that the technical steps of an enterocystoplasty can be satisfactorily and effectively performed laparoscopically.
Afforestation Alters the Composition of Functional Genes in Soil and Biogeochemical Processes in South American Grasslands

ABSTRACT Soil microbes are highly diverse and control most soil biogeochemical reactions. We examined how microbial functional genes and biogeochemical pools responded to the altered chemical inputs accompanying land use change. We examined paired native grasslands and adjacent Eucalyptus plantations (previously grassland) in Uruguay, a region that lacked forests before European settlement. Along with measurements of soil carbon, nitrogen, and bacterial diversity, we analyzed functional genes using the GeoChip 2.0 microarray, which simultaneously quantified several thousand genes involved in soil carbon and nitrogen cycling. Plantations and grassland differed significantly in functional gene profiles, bacterial diversity, and biogeochemical pool sizes. Most grassland profiles were similar, but plantation profiles generally differed from those of grasslands due to differences in functional gene abundance across diverse taxa. Eucalypts decreased ammonification and N fixation functional genes by 11% and 7.9% (P < 0.01), which correlated with decreased microbial biomass N and more NH4+ in plantation soils. Chitinase abundance decreased 7.8% in plantations compared to levels in grassland (P = 0.017), and C polymer-degrading genes decreased by 1.5% overall (P < 0.05), which likely contributed to 54% (P < 0.05) more C in undecomposed extractable soil pools and 27% less microbial C (P < 0.01) in plantation soils. In general, afforestation altered the abundance of many microbial functional genes, corresponding with changes in soil biogeochemistry, in part through altered abundance of overall functional gene types rather than simply through changes in specific taxa. Such changes in microbial functional genes correspond with altered C and N storage and have implications for long-term productivity in these soils.
Extra-Large G Proteins Expand the Repertoire of Subunits in Arabidopsis Heterotrimeric G Protein Signaling1[OPEN]

The three GTP-binding proteins function within the heterotrimeric G protein complex, increasing the diversity of possible heterotrimer combinations. Heterotrimeric G proteins, consisting of Gα, Gβ, and Gγ subunits, are a conserved signal transduction mechanism in eukaryotes. However, G protein subunit numbers in diploid plant genomes are greatly reduced as compared with animals and do not correlate with the diversity of functions and phenotypes in which heterotrimeric G proteins have been implicated. In addition to GPA1, the sole canonical Arabidopsis (Arabidopsis thaliana) Gα subunit, Arabidopsis has three related proteins: the extra-large GTP-binding proteins XLG1, XLG2, and XLG3. We demonstrate that the XLGs can bind Gβγ dimers (AGB1 plus a Gγ subunit: AGG1, AGG2, or AGG3) with differing specificity in yeast (Saccharomyces cerevisiae) three-hybrid assays. Our in silico structural analysis shows that XLG3 aligns closely to the crystal structure of GPA1, and XLG3 also competes with GPA1 for Gβγ binding in yeast. We observed interaction of the XLGs with all three Gβγ dimers at the plasma membrane in planta by bimolecular fluorescence complementation. Bioinformatic and localization studies identified and confirmed nuclear localization signals in XLG2 and XLG3 and a nuclear export signal in XLG3, which may facilitate intracellular shuttling. We found that tunicamycin, salt, and glucose hypersensitivity and increased stomatal density are agb1-specific phenotypes that are not observed in gpa1 mutants but are recapitulated in xlg mutants. Thus, XLG-Gβγ heterotrimers provide additional signaling modalities for tuning plant G protein responses and increase the repertoire of G protein heterotrimer combinations from three to 12. The potential for signal partitioning and competition between the XLGs and GPA1 is a new paradigm for plant-specific cell signaling.
Choice of time scale and its effect on significance of predictors in longitudinal studies

Time‐to‐event regression is a frequent tool in biomedical research. In clinical trials this time is usually measured from the beginning of the study. The same approach is often adopted in the analysis of longitudinal observational studies. However, in recent years there has appeared literature making a case for the use of the date of birth as a starting point, and thus utilize age as the time‐to‐event. In this paper, we explore different types of age‐scale models and compare them with time‐on‐study models in terms of the estimated regression coefficients they produce. We consider six proportional hazards regression models that differ in the choice of time scale and in the method of adjusting for the years before the study. By considering the estimating equations of these models as well as numerical simulations we conclude that correct adjustment for the age at entry is crucial in reducing bias of the estimated coefficients. The unadjusted age‐scale model is inferior to any of the five other models considered, regardless of their choice of time scale. Additionally, if adjustment for age at entry is made, our analyses show very little to suggest that there exists any practically meaningful difference in the estimated regression coefficients depending on the choice of time scale. These findings are supported by four practical examples from the Framingham Heart Study. Copyright © 2006 John Wiley & Sons, Ltd.
Peptides and proteins in a confined environment: NMR spectra at natural isotopic abundance

Confinement of proteins and peptides in a small inert space mimics the natural environment of the cell, allowing structural studies in conditions that stabilize folded conformations. We have previously shown that confinement in polyacrylamide gels (PAGs) is sufficient to induce a change in the viscosity of the aqueous solution without changing the composition and temperature of the solvent. The main limitation of a PAG to run NMR experiments in a confined environment is the need for labelling the peptides. Here we report the use of the agarose gel to run the NMR spectra of proteins and peptides. We show that agarose gels are completely transparent in NMR experiments, relieving the need for labelling. Although it is necessary to expose biomolecules to fairly high temperatures during sample preparation, we believe that this is not generally an obstacle to the study of peptides, and found that the method is also compatible with temperature‐resistant proteins. The mesh of agarose gels is too wide for direct effects of confinement on the stability of proteins but confinement can be easily exploited to interact the proteins with other reagents, including crowding macromolecules that can eventually lead to fold stabilization. The use of these gels is ideally suited for low‐temperature studies; we show that a very flexible peptide at subzero temperatures is stabilized into a well‐folded conformation. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Information hiding using whitespace technique in Microsoft word

Steganography is a data hiding technique that allows data to be hidden behind another data such as image, audio, and text. Among these three common media, text steganography that is referred to hiding the secret message behind other text, is known to be the most difficult approach. This is due to its lack of redundant information, comparing to the other media such as image, audio and video to hide the secret message. To overcome this problem, a modified whitespace technique has been developed to embed the secret message within the text without significant changes on the text file. In addition, the proposed technique makes a degree of difficulties for the attacker to decode the secret message using random shuffled spaces between the word spaces and different key for embedding the secret message.
Efficacy of ultrasound and nerve stimulation guidance in peripheral nerve block: A systematic review and meta‐analysis

Evidence was controversial about whether nerve stimulation (NS) can optimize ultrasound guidance (US)‐guided nerve blockade for peripheral nerve block. This review aims to explore the effects of the two combined techniques. We searched EMBASE (from 1974 to March 2015), PubMed (from 1966 to Mar 2015), Medline (from 1966 to Mar 2015), the Cochrane Central Register of Controlled Trials and clinicaltrials.gov. Finally, 15 randomized trials were included into analysis involving 1,019 lower limb and 696 upper limb surgery cases. Meta‐analysis indicated that, compared with US alone, USNS combination had favorable effects on overall block success rate (risk ratio [RR] 1.17; confidence interval [CI] 1.05 to 1.30, P = 0.004), sensory block success rate (RR 1.56; CI 1.29 to 1.89, P < 0.00001), and block onset time (mean difference [MD] –3.84; CI –5.59 to –2.08, P < 0.0001). USNS guidance had a longer procedure time in both upper and lower limb nerve block (MD 1.67; CI 1.32 to 2.02, P < 0.00001; MD 1.17; CI 0.95 to 1.39, P < 0.00001) and more patients with anesthesia supplementation (RR 2.5; CI 1.02 to 6.13, P = 0.05). USNS guidance trends to result in a shorter block onset time than US alone as well as higher block success rate, but no statistical difference was demonstrated, as more data are required. © 2017 IUBMB Life, 69(9):720–734, 2017
A novel harvesting method for cultured cells using iron‐cross‐linked alginate films as culture substrates

The present study was conducted to assess the efficiency of a novel cell‐harvesting method involving dissolution of the culture substrate composed of Fe‐alginate (ferric‐ion‐cross‐linked alginate). Cell harvesting is an essential step for recovery of cultured adherent cells, but conventional methods such as trypsinization or scraping cause considerable damage to the cells. We therefore devised an original method for harvesting cultured cells using Fe‐alginate films as a culture substrate and then retrieving the cells by disintegration of the alginate gel. Fe‐alginate was easily dissolved under physiological conditions by exchange of cross‐linked ions using chelating agents such as citrate. The effects of this cell‐harvesting method were investigated in comparison with trypsinization and scraping. Cells harvested by dissolution of the Fe‐alginate substrate showed high viability and metabolic activity, high recovery rate on subculture, a low degree of membrane damage with superior expression of cell adhesion molecules (β1 integrin and N‐cadherin), high resistance to oxidative stress, and high viability, metabolic activity and recovery rate after cryopreservation, in contrast with the cells harvested by trypsinization or scraping from tissue‐culture polystyrene substrates. These results suggest that our new system involving dissolution of Fe‐alginate culture substrate is effective for cell harvesting and may be advantageous for biomedical applications.
Direct Democracy and Voter Mobilization

>> Previous research has found that the campaigns of candidates running for office provide information to voters and can increase turnout. Scholarly research has also found that states with initiatives and referendums appearing on the ballot have higher voter turnout, especially in midterm elections. However, actual initiative campaigns are rarely measured. Drawing on national survey data and state contextual factors, we use a multilevel modeling strategy to test whether Americans are more likely to vote in recent midterm and presidential elections when there is increased spending in initiative and candidate campaigns, as well as more frequent use of direct democracy. The research includes a number of methodological advancements from earlier work on turnout and direct democracy (including a control for endogeneity) by restricting the analysis to initiative states only. The analysis suggests initiative campaigns not only increase individual level turnout but also especially benefit the lower educated.
Heat Shock Protein 90 in Plants: Molecular Mechanisms and Roles in Stress Responses

The heat shock protein 90 (Hsp90) family mediates stress signal transduction, and plays important roles in the control of normal growth of human cells and in promoting development of tumor cells. Hsp90s have become a currently important subject in cellular immunity, signal transduction, and anti-cancer research. Studies on the physiological functions of Hsp90s began much later in plants than in animals and fungi. Significant progress has been made in understanding complex mechanisms of HSP90s in plants, including ATPase-coupled conformational changes and interactions with cochaperone proteins. A wide range of signaling proteins interact with HSP90s. Recent studies revealed that plant Hsp90s are important in plant development, environmental stress response, and disease and pest resistance. In this study, the plant HSP90 family was classified into three clusters on the basis of phylogenetic relationships, gene structure, and biological functions. We discuss the molecular functions of Hsp90s, and systematically review recent progress of Hsp90 research in plants.
Filling the Tank: Keeping Antitumor T Cells Metabolically Fit for the Long Haul

Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions. T-cell activation and consequent effector function are cellular states characterized by extreme metabolic demands, and activation in the context of insufficient metabolic substrates results in anergy or regulatory differentiation. Thus, T cells must endure both immunosuppression (co-inhibitory molecule ligation, regulatory T cells, and suppressive cytokines) but also a sort of metabolic suppression in the TME. Here I will review the general features of the TME, identify the metabolic demands of activated effector T cells, discuss the known metabolic checkpoints associated with intratumoral T cells, and propose strategies for generating superior antitumor T cells, whether in vitro for adoptive cell therapy or through in vivo reinvigoration of the existing immune response. Cancer Immunol Res; 4(12); 1001–6. ©2016 AACR.
A cylindrical shaped theranostic applicator for percutaneous microwave ablation

The design of a minimally invasive surgery tool for the detection and treatment of cancerous tissue is presented. The planar structure is based on spiral resonators, with an operating frequency range from 4 GHz to 6 GHz, excited by a conventional coplanar waveguide to, firstly, extract resonance shifts to gain information about permittivity changes in the surrounded tissue. As second feature, tumorous cells can be eradicated by performing thermal ablation. The focus of this work lies in the integration of the structure in a needle-like tool with a diameter of 2.1 mm for percutaneous interventions by using a flexible substrate that is rolled into the desired shape. Full wave simulations of the planar and cylindrical structures are presented. Furthermore, initial measurements are performed to evaluate the detection and treatment mode characteristics. A dimension of the ablation zone of 2.9 cm3 is achieved with an input power of 20 W for 4min exposure.
Moving In and Out of Welfare and Work: The Influence of Regional Socioeconomic Circumstances on Economic Disconnection Among Low-Income Single Mothers

An increasing proportion of low-income single mothers are experiencing periods of economic disconnection, defined as receiving no cash income from welfare or work. Most research on disconnection has focused on personal attributes as risk factors for experiencing disconnection at a static point in time. This study adopts a dynamic perspective and broadens the existing set of determinants by adding regional socioeconomic characteristics to explain changes in status. Results from multivariate survival analyses demonstrate that residence in a disadvantaged county is associated with an increased risk of becoming disconnected. State-level policies, as opposed to county socioeconomic characteristics, have stronger influences on movements out of disconnection. The findings from the analyses provide a base for policy discussions about helping this vulnerable population.
Optimization of efficiency in the glyoxalase pathway.

A quantitative kinetic model for the glutathione-dependent conversion of methylglyoxal to D-lactate in mammalian erythrocytes has been formulated, on the basis of the measured or calculated rate and equilibrium constants associated with (a) the hydration of methylglyoxal, (b) the specific base catalyzed formation of glutathione-(R,S)-methylglyoxal thiohemiacetals, (c) the glyoxalase I catalyzed conversion of the diastereotopic thiohemiacetals to (S)-D-lactoylglutathione, and (d) the glyoxalase II catalyzed hydrolysis of (S)-D-lactoylglutathione to form D-lactate and glutathione. The model exhibits the following properties under conditions where substrate concentrations are small in comparison to the Km values for the glyoxalase enzymes: The overall rate of conversion of methylglyoxal to D-lactate is primarily limited by the rate of formation of the diastereotopic thiohemiacetals. The hydration of methylglyoxal is kinetically unimportant, since the apparent rate constant for hydration is (approximately 500-10(3))-fold smaller than that for formation of the thiohemiacetals. The rate of conversion of methylglyoxal to (S)-D-lactoylglutathione is near optimal, on the basis that the apparent rate constant for the glyoxalase I reaction (kcatEt/Km congruent to 4-20 s-1 for pig, rat, and human erythrocytes) is roughly equal to the apparent rate constant for decomposition of the thiohemiacetals to form glutathione and methylglyoxal [k(obsd) = 11 s-1, pH 7]. The capacity of glyoxalase I to use both diastereotopic thiohemiacetals, versus only one of the diastereomers, as substrates represents a 3- to 6-fold advantage in the steady-state rate of conversion of the diastereomers to (S)-D-lactoylglutathione. (ABSTRACT TRUNCATED AT 250 WORDS)
Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer.

PURPOSE Lapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER-2/ErbB2), is effective against HER-2-positive locally advanced or metastatic breast cancer (MBC). This phase III trial evaluated the efficacy of lapatinib in HER-2-negative and HER-2-uncharacterized MBC. PATIENTS AND METHODS Women with MBC were randomly assigned to first-line therapy with paclitaxel 175 mg/m(2) every 3 weeks plus lapatinib 1,500 mg/d or placebo. A preplanned retrospective evaluation of HER-2 status was performed using fluorescence in situ hybridization and immunohistochemistry. The primary end point was time to progression (TTP); secondary end points were objective response rate (ORR), clinical benefit rate (CBR), event-free survival (EFS), and overall survival (OS). RESULTS In the intent-to-treat population (n = 579), there were no significant differences in TTP, EFS, or OS between treatment arms, although differences in ORR and CBR were noted. In 86 HER-2-positive patients (15%), treatment with paclitaxel-lapatinib resulted in statistically significant improvements in TTP, EFS, ORR, and CBR compared with paclitaxel-placebo. No differences between treatment groups were observed for any end point in HER-2-negative patients. The most common adverse events were alopecia, rash, and diarrhea. The incidence of diarrhea and rash was significantly higher in the paclitaxel-lapatinib arm. The rate of cardiac events was low, and no difference was observed between treatment arms. CONCLUSION Patients with HER-2-negative or HER-2-untested MBC did not benefit from the addition of lapatinib to paclitaxel. However, first-line therapy with paclitaxel-lapatinib significantly improved clinical outcomes in HER-2-positive patients. Prospective evaluation of the efficacy and safety of this combination is ongoing in early and metastatic HER-2-positive breast cancer patients.