br Results br Discussion and

Results

Discussion and recommendations

Conclusion
The research acknowledges that despite following similar Islamic faiths, the seven Muslim corticotropin-releasing factor interviewed managed to adapt with the use of Western sitting toilets without any major difficulty. Muslims in Australia may have different interpretations of Islamic teachings while living in a Western context. This does not determine one׳s religiousness but one׳s ability to adapt themselves through minor modifications or behavioural changes to comply with their traditional traditions or religious faiths. The contribution of this exploratory study is limited and may not be applicable to those of different cultural or religious backgrounds because of its small sample from one focus group and within one city. Further research using larger population sample at state or national level and with participants from different cultural or religious backgrounds may provide better understanding on the feasibility and suitability of the use of squat toilets and shattaf in the country. However, the recommendations from the research findings provide useful new knowledge to architects, builders, and home renovators who previously are not aware of these variations of toilet habits. Future research and design explorations by researchers, architects and designers are essential in order to offer universal design solutions for culturally adaptable and inclusive toilet systems that can accommodate the needs of the users from diverse backgrounds and traditions.

Acknowledgements

In this study we demonstrated that astrocytes exposed

In this study, we demonstrated that astrocytes exposed to ACM undergo de-differentiation to multipotent NSPCs which can re-differentiate into neurons, astrocytes, and oligodentrocytes. Cyanine3.5 carboxylic acid Whereas blockade of Shh biological functions in ACM does not result in astrocyte de-differentiation to multipotent NSPCs (because they can only differentiate into astrocytes and oligodentrocytes) even though they also form neurosphere-like structures. The differentiation diversity may be largely due to distinct properties of neurosphere-forming cells and the distinct phenotype of neurosphere cells. This result revealed that lack of Shh signaling may be insufficient to enhance astrocyte reprogramming and enter a truly less differentiated state. Rather, they only generate intermediate or more restricted precursor cells such as glial-restricted precursor cells, oligodendrocyte precursor cells, and O2A glial progenitors. It has been documented that astrocytes could not de-differentiate fully into NSCs directly when induced under appropriate signal molecules, rather they might undergo progressive rejuvenation (Dai et al., 2001; Buffo et al., 2005; Sharif et al., 2007). In corroboration of the assumption in the present study we further conducted the examination of multiple signaling pathway components Ptc, Gli2, and Cyclin D1 expression in the considerable complicated event. Our data suggest that Shh has a synergistic effect with other molecule signaling in ACM on Ptc expression, since elevation of Ptc expression greatly enhances Shh signal transduction to Gli2 by a protein complex composed Fu, SuFu, Cos-2, and cytoskeletons which further regulates transcription of certain molecules such as ErbB2, Wnt1 and Bmi1 (Liu and Rao, 2004; Sher et al., 2011; Yang et al., 2011). These molecules are intimately linked to cell reprogramming, disruption of Cyanine3.5 carboxylic acid arrest, cell cycle re-entry, and cell lineage specification. The above‐mentioned events occur through up-regulation of Cyclin D1 mRNA and protein levels, which allow mature cells to de-differentiate and subsequently re-enter the cell cycle. The important downstream molecule of Gli2 transcriptional activator thus was further examined. Coincidentally, immunocytochemistry and western blot analyses showed Cyclin D1 expression patterns are similar to that of Gli2. Cyclin D1 was up-regulated in ACM-treated astrocytes. In contrast, the administration of Shh n-Ab to the astrocytes in the presence of ACM failed to result in any significant increase of Cyclin D1. Of note, Shh alone also cannot result in the up-regulation of Cyclin D1 expression either. These data imply, but do not prove, that other molecules in ACM may be required for the induction of conversion from astrocyte to NSCs.
Collectively, this study has evidenced that apart with Shh signaling, there is involvement of multiple molecular subgroups in the reversion of astrocyte to the un-differentiated states, implying that there could be numerous mechanisms that lead to astrocyte de-differentiation in vitro. The complete conversion of astrocytes to NSPCs could still be due to acquisition of additional unknown signaling compensations besides Shh responsible for activation of molecule pathways in astrocyte rejuvenation. Therefore it is extremely important to seek these molecules for induction of astrocyte de-differentiation into NSPCs. Therefore, the present findings have important implications for neural progenitors of astrocytic origin as one of the most promising alternative sources for autologous transplantation for clinical repair of CNS deficits.

Disclosure statement

Acknowledgments
We thank Dr. Wade, Brandy Elizabeth from Emory University for critical reading of the manuscript. This work was supported by the Natural Science Foundation of China (Grant No. 30973088), and National Key Basic Research and Development Project (the 973 Project, 2011CB504402).

Introduction
Hematopoietic stem cells (HSC) have been used in clinical transplantation for decades. Transplantation of autologous marrow is used to treat patients with different neoplastic diseases (Armitage and Gale, 1989; Copelan, 2006). Prior to bone marrow transplantation the patient will receive high dose chemotherapy, and attempts are made to deplete the marrow of malignant cells, but the remaining cancer cells still lead to relapse in many patients. Allogeneic transplantation using bone marrow from human leukocyte antigen (HLA) identical family donors gives the best clinical outcome in patients with several hematopoietic malignancies (Armitage, 1992; Devetten and Armitage, 2007). Unfortunately such donors are often not available, and the patient has to undergo transplantation with HLA discordant bone marrow from a family donor, or marrow obtained from a donor identified through a marrow donor registry. Transplantation of these bone marrows is more likely to cause life-threatening graft-versus-host disease. In both these settings, if HSC could be made from the patient\’s own cells, presumably they would be the HSC best suited to restore the blood and immune system with no risk of cancer cell contamination or alloimmune side effects.

We analyzed whether DLK PREF that was

We analyzed whether DLK1(PREF1), that was firstly identified as a putative marker for murine preadipocytes (Smas and Sul, 1993), could be used as additional marker to characterize human ASC. We found that DLK1(PREF1) is highly expressed in human ASC. The DLK1(PREF1) protein levels were similar in human ASC proliferating in PM4 medium and in density-arrested G0/G1-phase ASC. In the course of adipogenic differentiation the DLK1(PREF1) protein level declined. DLK1(PREF1) was almost undetectable in adipocytes 14days after the induction of adipocyte differentiation. Thus DLK1(PREF1) is expressed in proliferating ASC, in density-arrested ASC, and most likely at early stages of adipogenic differentiation but completely downregulated in human adipocytes. During adipogenic differentiation of MEFs (mouse embryonic fibroblasts) the DLK1(PREF1) protein levels are relatively low in density arrest before differentiation, transiently increased at days 1 and 2, and then decreased and were undetectable at day 5 after conversion into adipocytes (Wang and Sul, 2009). Similar in adipogenesis of the preadipocyte cell line NIH 3 T3 L1 the DLK1(PREF1) protein levels are low in density arrest before differentiation and transiently increase until day 2–3 (Garces et al., 1999). When these 4-ethylphenyl sulfate cease clonal expansion and enter terminal adipogenic differentiation (Farmer, 2006), the DLK1(PREF1) protein levels decrease but membranous forms of DLK1(PREF1) are detectable until day 5 (Garces et al., 1999). Thus certain forms of DLK1(PREF1) protein are still present at early stages of terminal adipogenic differentiation and may contribute to adipocyte differentiation (Garces et al., 1999). DLK1(PREF1) has been identified as a negative regulator of adipocyte differentiation in mouse preadipocytes (Smas and Sul, 1993). Moreover, in its active form, DLK1(PREF1) was shown to function in an autocrine and paracrine manner as soluble factor to inhibit differentiation of murine multipotent MSC into adipocytes, osteoblasts and chondrocytes (Wang and Sul, 2009; Wang et al., 2010). This suggests that DLK1(PREF1) has a general role in keeping mouse precursor cells in an undifferentiated state. In the present study we found that DLK1(PREF1) functions as negative regulator of adipogenesis in human ASC. Previous studies have identified DLK1(PREF1) as regulator of differentiation in human BM MSC (Abdallah et al., 2004; Jing et al., 2009) and CB MSC (Kluth et al., 2010). DLK1(PREF1) was used as a marker to distinguish human unrestricted somatic stem cells and CB MSC (Kluth et al., 2010). Moreover, DLK1(PREF1) was employed as surface marker for the isolation and differentiation of chondrogenic cells derived from human embryonic stem cells (Harkness et al., 2009). DLK1(PREF1) is also involved in additional differentiation processes in rodent cells, including haematopoiesis (Moore et al., 1997), pancreatic islet cell differentiation (Carlsson et al., 1997), Schwann cell differentiation (Costaglioli et al., 2001), hepatic cell differentiation (Tanimizu et al., 2004), and differentiation of muscle satellite cells. Moreover, DLK1(PREF1) is expressed in thymocytes and neuroblastoma cells [reviewed in Sul, 2009]. Thus DLK1(PREF1) should be used in combination with additional markers to distinguish ASC from MSC and other cell types, especially in combination with the CD34+ and CD31− immunophenotype, as considered earlier (Gesta et al., 2007).
Studies in mice suggest that the age, depot site and sex of the donor can influence the features and functionality of the derived ASC (Cartwright et al., 2010; Gesta et al., 2006; Majka et al., 2010). Clinical studies found a correlation between donor age and differentiation capacity of the given ASC (Madonna et al., 2011; Schipper et al., 2008; Zhu et al., 2009). In humans also an influence of the BMI (van Harmelen et al., 2003) and fat depot origin (Tchkonia et al., 2002, 2007) on ASC features was shown. In the present study, we isolated ASC from subcutaneous adipose tissue pads of four different women with an age between 30 and 47years and a BMI between 22 and 27kg/m2. No differences in the analyzed cell surface marker patterns were found between the ASC from the abdominal subcutaneous depots of the different donors. Moreover, all ASC populations had a high capacity to differentiate into adipocytes in vitro, as demonstrated by the formation of high levels of four terminal adipogenic differentiation products, FABP4, adiponectin, leptin and triglycerides. This suggests that the relatively small differences in age and BMI between our four donors did not account for major differences in these ASC features. We detected however differences in the strength of the adipogenic maturation at the level of single ASC isolated from the same depot. This was reflected by the difference in the quantity and size of lipid droplets formed 20days after the induction of adipogenesis (Fig. 2H, compare white and yellow arrows). These findings are in keeping with the differences in the single cell FABP4 protein level (Fig. 2A, compare white and yellow arrows). These data suggest that there may be heterogeneity regarding the adipogenic capacity of ASC within the same depots. Almost all passage 5 ASC stained strongly positive for the marker composition DLK1(PREF1)+/CD105+/CD90+/CD34+/CD31−/FABP4−. However, this marker combination cannot distinguish ASC with high or low adipogenic capacity. Evidence for differences between ASC populations cloned from a single human subcutaneous fat depot regarding the differentiation capacity was previously shown (Kirkland et al., 1993; Tchkonia et al., 2005; Zimmerlin et al., 2010). Common observations in our study were islets of strongly differentiated ASC surrounded by areas of weaker differentiated ASC. This could, for example, result from differences in the autocrine/paracrine micromilieu caused by a different cell density. Such findings could mirror the existence of different subtypes of ASC in subcutaneous fat depots in vivo, as discussed previously (Gesta et al., 2007). More studies are necessary to better understand these observations.

br Materials and Methods br Results br Discussion At present

Materials and Methods

Results

Discussion
At present time the majority of genetic disorders involving haploinsufficiency in a single gene, such as Dravet syndrome, have no adequate treatment. Only partially effective symptomatic therapy targeted at seizure reduction is now available for Dravet patients. Furthermore, although initially Dravet syndrome was considered an epileptic encephalopathy (Wolff et al., 2006), recent studies in Dravet patients have shown that some aspects of the syndrome may arise independently of seizures and thus cannot be addressed by anticonvulsants (Nabbout et al., 2013). In rat models, siRNA-mediated Scn1a knockdown in adult animals selective for basal forebrain induced cognitive impairment without seizures (Bender et al., 2013). Notably, upregulation of the remaining normal copy of the damaged gene has the potential to improve all disease manifestations and represents an appealing therapeutic strategy.
In our in vitro and in vivo experiments we were able to upregulate SCN1A expression by using AntagoNATs (oligonucleotide-like compounds) that block the activity of SCN1ANAT. While AntagoNAT treatment upregulated SCN1A, it did not affect >90% of all expressed genes, including other highly homologous sodium channel subunits and genes immediately adjacent to SCN1A on the chromosome (Fig. 5; Supplementary File 1).
Furthermore, we have demonstrated that SCN1A upregulation can be effective in a mouse model of Dravet if applied at some time point after birth, when genetic disorders are usually diagnosed. Our experiments in a mouse model harboring a known Dravet mutation demonstrate that Scn1a upregulation during PW 7–11 leads to improvements in several aspects of disease phenotype, including frequency and severity of seizures. We observed that a 25% increase in tsa inhibitor Supplier Scn1a levels was sufficient to elicit a 70% reduction in seizure frequency and a decrease in seizure severity (Fig. 8). Additionally, upregulation of brain Scn1a levels was associated with decreased sensitivity to heat-induced seizures, which represent a hallmark of Dravet syndrome. AntagoNAT treatment also normalized increased firing threshold and reduced firing frequency of inhibitory interneurons observed in Dravet models (Fig. 9, Oakley et al., 2011; Yamakawa, 2011; Tai et al., 2014; Ogiwara et al., 2013). Importantly, in rat models with RNAi-induced Scn1a knockdown, disruption in neuronal firing was correlated with performance in working memory task (Bender et al., 2016). This underscores the importance of normalizing the neuronal firing for the treatment of cognitive deficits associated with Dravet syndrome. Overall, significant improvements of seizure phenotype and neuronal electrophysiology observed in our experiments provide an integral indicator that Scn1a upregulation achieved using AntagoNATs can adequately address the excitation/inhibition imbalance occurring in Dravet brain.
Besides seizures, another known aspect of Dravet syndrome is increased mortality (Dravet, 2011). Similar to human disease, the death rate in the Scn1aE1099X/+ mice peaks in early development (with approximately 70% of mice dying before PW7) and then stabilizes at relatively low levels. Additionally, Dravet mice are generally smaller and have elevated sensitivity to surgical interventions compared to WT. For these reasons, in our experiments EEG electrode implantation and IT injection of AntagoNATs were conducted at PW7–11, past the critical period. As a result, the small numbers of deaths observed in our studies did not allow for a conclusive statistical analysis at this time. Consequently, the reported results are only relevant to the more mildly affected surviving mice or potentially Dravet patients older than 3years. Further experiments, in which AntagoNAT treatment will be started prior to the PW3–5 critical window are needed to verify whether AntagoNAT-mediated upregulation of SCN1A could reduce the early mortality rate. Due to technical difficulties, these experiments would likely require development of an alternative administration route.

Despite all these observations linking bacteria to intrinsic

Despite all these observations linking bacteria to intrinsic serotonin synthesis, very little is understood regarding why, how, and what are the consequences of the microbiome\’s influence on the host\’s neurotransmitter levels and its manipulation, and vice versa. Most studies focus on the influence of the microbiome on changes to the host\’s production of these molecules, while very few examine the effects these molecules have on bacteria. It was observed that serotonin was able to stimulate growth of specific bacteria in culture (Oleskin et al., 1998), and some virulent bacteria can use neurotransmitters such as GDC-0199 Supplier and norepinephrine to activate virulence genes (Clarke et al., 2006). Both of these phenomena are linked to bacterial quorum sensing (QS), which is, in bacteria, a phenomenon when populations reach a specific threshold they communicate with organisms in their surroundings by releasing small diffusible quorum sensing molecules (QSMs). The QSMs then bind to regulatory proteins, causing a conformational change and allowing the protein to bind to DNA and initiate the transcription of virulence factors (Fig. 1). Herein, we hypothesized that bacteria are able to interact with host serotonin molecules and exploit them as a bacterial QSMs. Specifically, through experiments conducted in vitro and in vivo in animal studies, we demonstrate for the first time that serotonin acts as a signaling molecule for the las regulatory QS system of Pseudomonas aeruginosa inducing, among other effects, serious pathogenicity in the host. P. aeruginosa has a well-studied QS network that relies on multiple QS pathways critical in activating Pseudomonas virulence including the las and rhl systems. This work helps explains how high levels of serotonin found in the gut, produced endogenously or by bacteria, can be linked to the host\’s health.

Materials and Methods

Results

Discussion
This study establishes serotonin\’s role as a bacterial quorum sensing molecule. Our cellular system data show that serotonin can activate the LasR QS pathway at μM concentrations (Fig. 3b). This finding is of great interest as physiological levels of serotonin in the digestive tract of healthy and diseased individuals is 10μM (Erspamer, 1966) and ~100μM (Miwa et al., 2001) respectively. The raised levels of serotonin in patients with Inflammatory Bowel Disease (IBD), combined with the insight that serotonin can activate QS pathways, may allow for better patient care and therapeutics. Additionally, the additive effects of serotonin combined with QSM (Fig. 3c) are relevant as bacteria exist naturally in the gut, thus it is highly likely that serotonin will co-exist with bacterial QSMs.
Previous reports have shown that virulence factor production, such as biofilm formation and protease production, are quorum-dependent (Waters et al., 2008, Valiente et al., 2007), which supports the increase in these factors seen when serotonin was administered in both our in vitro (Fig. 4) and in vivo (Figs. 2, 5) experiments as serotonin activating the LasR QS system. In vitro, our results show that serotonin mimics the effects of exogenous QSM addition in JP2 cells\’ biofilm formation (Fig. 4C–D), indicating that serotonin acts as a bacterial signaling molecule that is capable of activating QS-regulated phenotypes. Our developed Pseudomonas infection model demonstrated that serotonin was able to activate Pseudomonas virulence in vivo, within the intestines of the mice (Figs. 2, 5). Within these experiments, there are two points of particular interest: in the absence of serotonin the JP2 mutant that cannot generate its own QSMs was not able to establish an infection, and the effects of PAO1 infection alone were similar to the effects of JP2 with serotonin. When administered the same CFU of JP2 cells compared to PAO1 cells, the JP2 mutant Pseudomonas did not establish any detectable colonies (Fig. S3B). This lack of infection is supported by the SEM images (Fig. 5A) and histology data (Fig. 5B–C). As the JP2 mutant is only lacking in QSM synthesis, this inability to establish an infection both supports the current literature that Pseudomonas virulence is QS dependent and allows for the assessment of restoration of function, specifically the ability to establish an infection. Thus when we restore the infectivity of JP2 by administering serotonin (Fig. S3B), it indicates that serotonin is fulfilling the role of a QSM. The infection with PAO1 alone and JP2 with serotonin resulted in similar levels of CFUs harvested from the intestines (Fig. S1D, S3B), which further supports serotonin\’s role as a QSM. This similarity between PAO1 alone and JP2 with serotonin is also noted in the histology data (Figs. 2B–C, 5B–C), with both exhibiting intestinal epithelial damage and villi destruction. These data further demonstrate serotonin\’s ability to restore function to the JP2 mutant lacking QSMs, providing greater evidence for its role as a QSM.

Stratifying patients according to the toxicity

Stratifying patients according to the toxicity risk and modulating EBRT dose would provide a valuable tool for personalized EBRT (). Many efforts have been made to develop assays capable of predicting susceptibility for the development of radiation injury that finally allow customization of EBRT protocols on an individual basis.
Indeed and as presented in this current volume of , Kerns and colleagues (), aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify novel genetic markers of toxicity. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency and rs7720298 on 5p15.2 with decreased urine stream. These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The authors mentioned that new moderate-penetrance genetic variants associated with radiotherapy toxicity have been identified. As we know, radiogenomics (RG) attempts to link germ line genotypic variations and clinical variability observed after EBRT. The aim of RG is to identify the order Microcystin-LR that underlie the inherited dissimilarities in phenotype (). However, this hypothesis does not assume that all of the phenotypic differences are due to germ line genetic alterations, but also epigenetic changes and other factors such as systemic treatment or tobacco use. Recently, DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identified differences associated with fibrosis. One region was characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (DGKA). Decreased DNA methylation at this enhancer was shown to enable recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and then capable to facilitate radiation-induced DGKA transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA showed pronounced effects on diacylglycerol-mediated lipid homeostasis with profibrotic fibroblast activation ().
As mentioned in a recent review by , pathway analyses incorporating different ‘omics’ approaches may be more efficient in identifying critical pathways than those based on single ‘omics’ data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of EBRT patients characterized by different mechanisms. In that way, monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) as a functional test can predict late toxicity after curative intent EBRT. We recently assessed the role of RILA as a predictor of breast fibrosis (bf+) after adjuvant breast EBRT in a prospective multicenter trial (). A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant EBRT were recruited at ten centers. RILA was assessed before EBRT by flow cytometry. Impact of RILA on bf+ (primary endpoint) or relapse was assessed using a competing risk method. With a median follow-up of 38.6months, grade ≥2 bf+ was observed in 64 pts (14%). A decreased incidence of grade ≥2 bf+ was observed for increasing values of RILA (p=0.012). No grade 3 bf+ was observed for patients with RILA ≥12%. Negative predictive value for grade ≥2 bf+ was equal to 91% for RILA ≥20% where the overall prevalence of grade ≥2 bf+ was estimated at 14%. A significant decrease in the risk of grade ≥2 bf+ was found if patients had no adjuvant hormonotherapy (sHR=0.31, p=0.007) and presented a RILA ≥12% (sHR=0.45, p=0.002). Different hypotheses to understand the mechanisms of inverse correlation between low radiation response of lymphocytes and the increase risk of developing late reaction after EBRT are currently under investigations: (i) Production of cytokines and inflammatory immune cells attraction to the irradiated tissue (); (ii) Protein and ROS production modification, enhanced genomic instability, terminal differentiation of fibroblasts and increased risk of fibrogenesis (); (iii) genetic defect in the DNA damage response, DNA repair reduction, increased genomic instability and increased premature terminal differentiation of fibroblasts ().

luciferin br Materials and methods br Acknowledgments We would like

Materials and methods

Acknowledgments
We would like to thank all members of the Imhof and Heun group for critical discussions and feedback and the anonymous reviewer for valuable comments and suggestions to improve the manuscript. Work in the lab of A.I. was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft (DFG; Projekt IM 23/9-1)) and the European Union (EpiGeneSys, 257082). Work in the lab of P.H. was sponsored by an ERC (ERC-2012-StG_20111109) grant (ERC-BioSynCen).

Data
In the data we included size exclusion chromatography data of soluble eADF4(C16) in a combination with light scattering revealing that the protein is monomeric before assembly (Fig. 1). A defined structural state is important before starting any kinetic study, since assemblies may significantly influence the kinetics by accelerating the nucleation (Fig. 2). The assembled mature fibrils were visualized by transmission luciferin microscopy (TEM) (Fig. 3) and atomic force microscopy (AFM) (Fig. 4), revealing fibrils typically 10nm in diameter and 1µm in lengths. Sonication led to significantly shorter fibrils, as shown by AFM, increasing the number of the active fibril ends. Sonicated fibrils can be used as seeds to by-pass nucleation in eADF4(C16) assembly (Fig. 5). We further show sedimentation kinetics of spider silk in the presence of different NaCl concentrations revealing very slow protein aggregation (Fig. 6) in comparison to the fast assembly triggered by phosphate ions [1], which indicates that ion masking events are less important for the protein-protein interation during spider silk assembly.

Material and methods

[describe in 3–5 bulleted points why this data is of value to the scientific community]
Experimental design, materials and methods
As described in ‘Determination of Supplier-to-Supplier and Lot-to-Lot Variability in Glycation of Recombinant Human Serum Albumin Expressed in Oryza sativa’ [1,2,3,5].

Materials
Chemicals, essentially FA-free pHSA (A3872 Lot#090M7001V, ≥99% purity), recombinant human serum albumin expressed in Saccharomyces cerevisiae (ScrHSA, Lot# SLBD2407, ≥99% purity, Albucult), O. sativa [OsrHSA, Lot# SLBC7527V (OsrHSA-sig-C), Lot# SLBG7405V (OsrHSA-sig-G), Lot# SLBH9636V (OsrHSA-sig-H) and Lot# SLBJ1196V (OsrHSA-sig-J) 100% purity, Cellastim] and Pichia pastoris (PprHSA, Lot# 080M1580V, ≥99% purity, Albagen) were sourced from Sigma-Aldrich (St. Louis, MO, USA). OsrHSA was also obtained from eEnzyme LLC (Gaithersburg, MD, USA) (OsrHSA-phy) (Lot# 20130110, >99% purity, Phyto-HSA), ScienCell Research Laboratories (Carlsbad, CA, USA) (OsrHSA-sci) (Lot# BJABAA42, ≥99% purity, Oryzogen) and amsbio LLC (Cambridge, MA, USA) (OsrHSA-ams) (Lot #20101008, >95% purity, ecoHSA). Recombumin (Lot# PDP100106) was donated by Novozymes Biopharma (Cambridge, MA, USA). Amicon Ultra 0.5ml 3000Da molecular weight cut-off (MWCO) centrifugal filter devices were purchased from Millipore (Billerica, MA, USA). Trypsin and chymotrypsin were Promega sequencing grade purchased from Fisher Scientific Canada (Ottawa, ON, Canada). Vivacon 500 10kDa molecular weight cut-off filters were from Sartorius Stadium Biotech North America (Bohemia, NY, USA).

Albumin sample preparation
Albumin samples were prepared as described previously [4]. Briefly, samples were buffer exchanged into 5mM sodium phosphate (pH 7.4), with Amicon Ultra 0.5ml 3000Da MWCO centrifugal filter devices after pre-rinsing the filters with buffer. Protein concentrations were measured using a nerves BCA assay kit (Sigma-Aldrich, St. Louis, MO, USA). Protein integrity after buffer exchange was assessed with 1-D SDS−PAGE using SYPRO Ruby protein stain (Molecular Probes, Eugene, OR, USA) and a Bio-Rad Molecular Imager Gel Doc XR+ system with Quantity One 1-D analysis software according to the manufacturer’s instructions (Bio-Rad, Mississauga, ON, Canada).

Liquid chromatography–mass spectrometry (LC–MS) analysis—Sample preparation

Further we sort the lipids into

Further, we sort the Amyloid β-Peptide (1-42) into annular and non-annual regions (Fig. 12). Finally, we plot the lipid-number mismatch and surface area per lipid mismatch of several asymmetric lipid membrane systems (Fig. 13). The design of the initial structures (Fig. 8) of the dimer protein and lipid bilayer systems is provided in Materials and Methods of the research article [1]. The data was created using in-house scripts (surround for annular and non-annular region identification, and a python script for sorting of DSSP output) [6,7], g-tools (a suite of analysis programs available through the GROMACs MD engine [8]) for secondary structure analysis, binding kinetics, and residue contact maps, and VMD [9] for visualization of structures.

Acknowledgments
This work was supported by the Robert A. Welch Research Foundation grant (D-1158), NIH grant (GM090897-02), National Science Foundation (ACI 1531594), Williams Endowment Fund of Trinity University, Texas Advanced Computing Center (TACC) for the use of Lonestar Cluster under the project (G-803132) “Protein Unfolding in Lipid Membranes”, and Texas Tech University High Performance Computing Center (TTU-HPCC). The authors acknowledge the valuable help of Dr. Andrey A. Gurtovenko of the Institute of Macromolecular Compounds, Russian Academy of Sciences for allowing us to use the published asymmetric PC/PS bilayer system and valuable advices on the simulation details of the PC/PS bilayer system.

Experimental design, materials and methods
All experimental design, materials and methods were based on reported paper [1]

Acknowledgment
This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP; Grant nos. NRF-2014K1A4A7A01074642), Gyeonggi-do, KISTI, and the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant no. HI12C1804)

Value of the data

Data
This data provides supporting information of the role of Notch signaling on osteoclast differentiation and function [1]. Notch signaling has been shown to regulate osteoclastogenesis negatively by Notch1 or positively by Notch2 [2]. To investigate whether Notch signaling affects osteoclast differentiation and spreading, we assessed the inhibitory potential of four GSIs from BMM to mature osteoclast forming period.

Experimental design, materials and methods

Acknowledgments
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (NRF-2014R1A2A2A01002531).

Value of the data

Data
C2C12 mouse myoblasts are used to perform in vitro analyses related to skeletal muscle as they express proteins involved with membrane depolarization, calcium (Ca2+) storage and release, and contraction [1,2]. Previously, it was shown that Ca2+ depletion prevented starvation-induced autophagy in cardiomyocytes [3]. In this report we present data on the degree of autophagic flux in differentiated C2C12 myotubes in response to acetylcholine and caffeine (two stimuli that can influence Ca2+ signaling and contraction).

Experimental design, materials and methods

Acknowledgments
This research was supported by funds (341256) provided by the Natural Sciences and Engineering Research Council of Canada (NSERC) to Joe Quadrilatero. Darin Bloemberg is the recipient of a NSERC postgraduate scholarship. NSERC did not participate in study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication.

Specifications table

Value of the data

Data
Among 175 A. niger/A. welwitschiae strains analyzed, we found four mPCR profiles (Fig. 1). Profile 1 (17%) highlights strains harboring the pks (shown in blue, 554bp), radH (blue, 328bp) and fum8 (blue, 128bp) genes. Profile 2 (3.5%) highlights strains harboring only genes involved in OTA biosynthesis (radH and pks). Profile 3 (51.5%) highlights strains harboring only the gene fum8. Profile 4 (28%) highlights strains not carrying the mycotoxigenic genes studied herein.

Si en los a os tanto las militantes del MLF

Si en los años 70, tanto las militantes del MLF como las de la UFA (algunas de ellas ligadas por fuertes simpatías con partidos de izquierda) estuvieron de acuerdo en no contaminar al feminismo con otras militancias, en una lucha por conseguir cierta escucha específica, en los años 80, y de la mano de las atemas, esto fue revisado. Así, muchas exmilitantes de la ufa pasaron tropisetron participar con más intensidad en las actividades de atem que en las de ofa (organización formada en los primeros años de la década de los 80 que nucleaba a feministas destacadas de los 70 y que reeditaba la revista Persona).
Sin embargo, por su parte, desde Persona (años 80) se insistió sobre aquel punto aprendido del feminismo radical, en un contexto que marcaba otras demandas: “La Organización Feminista Argentina es una institución sin fines de lucro, ni partidismo político, que nos nuclea a las mujeres sin discriminación alguna con el fin de trabajar para el mejoramiento de nuestra condición en lo social, jurídico y económico” (Persona, abril 1980, folleto abrochado a la revista, sin paginación).
Persona, en marzo de 1982, en su editorial redoblaba la apuesta y sostenía:
El contrapunto hace evidente que las diferencias entre ambas escrituras se volvieron insoslayables. Las atemas enunciaron y enfatizaron un aspecto del feminismo que estuvo ausente en las definiciones de las militantes de los 70 y fue rechazado por ciertas estelas de aquel feminismo: una contextualización de la lucha feminista y un posicionamiento político. Desde Brujas, afirmaron que: “Contextualizar el movimiento feminista es una necesidad que marca su crecimiento. El feminismo debe contextuar (sic.) sus objetivos y sus luchas en el lugar en que actúa. En Argentina, el feminismo debe tomar posiciones antiimperialistas, a favor de los derechos humanos y de la lucha de clases” (Brujas, año 1, núm. 3, p. 7; las cursivas son nuestras). En distintos números de Brujas se insistió en remarcar el carácter anticapitalista y tercermun- dista latinoamericano en contexto posdictatorial del feminismo que ellas proponían. Brujas afirmó que el movimiento feminista, “como movimiento político y transformador, plantea objetivos y propuestas que se relacionan con el conjunto de la sociedad [pues] es necesario construir una sociedad sin relaciones jerárquicas. Tal pretensión lleva al feminismo a cuestionar la propiedad privada, las opresiones nacionales, de clase, de raza, de etnia” (Brujas, año 1, núm. 3, p. 7; las cursivas son nuestras).
María Elena Oddone cuenta en su autobiografía algunos de los desencuentros que se produjeron con las militantes feministas en los albores de los 80. Bajo el título El feminismo y las izquierdas, escribió una crítica acre a bladder la participación de las feministas en la política nacional que experimentaba la alegría y la esperanza del retorno a la democracia. En aquel escenario político, el reclamo incansable de las Madres de Plaza de Mayo por la aparición de los detenidos/as o desaparecidos/as de la dictadura militar marcaba el escenario político local. Oddone denunció lo que entendía como un embelesamiento de las nuevas militantes feministas por las Madres, y propuso entonces apoyar a las madres de los soldados muertos por la subversión. Así, tras la huella de sus posiciones políticas, nunca asumidas plenamente como tales, María Elena Oddone fue expulsada de varios espacios de militancia feminista a raíz no sólo de esta propuesta, sino de otras de similar talante (Oddone 2001). Por su parte, las atemas, después de estos primeros momentos de confrotación, desde las páginas de Brujas, guardaron un silencio casi sepulcral respecto del feminismo anterior. Se hacía evidente que las hebras con las cuales tejer la genealogía del feminismo argentino no eran del todo firmes o deseables a la mirada de las atemas.

Es un lugar común del discurso académico, pero también del discurso político, afirmar o sugerir que el principal obstáculo para la constitución del movimiento feminista en la Argentina fue otro movimiento, el peronista. Dicha operación de pensamiento, por otra parte, no sólo se aplica a las relaciones históricas del peronismo con el feminismo, sino que resulta cara a múltiples interpretaciones de las consecuencias que produjo la irrupción del fenómeno peronista. El peronismo, para la intelectualidad progresista, sigue siendo, a su manera, objeto de preguntas que, si recaen en la figura del fenómeno —algo más que una fenomenología entendida como las condiciones de aparición—, dan cuenta de que se entiende poco o nada. En cambio, si abonan la cuestión peronista, puede decirse que se está frente a verdaderas preguntas. En ambos casos, el peronismo —parodiando a Vovelle— sigue siendo una cantera abierta que no deja de suscitar inquietudes políticas e intelectuales. Ahora, si bien esa conexión entre el menos (-) del feminismo y el más (+) del peronismo no asume hoy la forma cruda o bienpensante que adquirió en los años 70 y 80, o el estilo amable y sutil presente en alguna ensayística de los 70 —como la Eva Perón ¿aventurera o militante? de Sebreli—, sigue siendo un presupuesto, en alto grado inexpugnable para el saber académico, que la política del peronismo hacia y con las mujeres afectó el ideal de una condición femenina volcada hacia una práctica militante feminista.

Con tal fin Ferrajoli analiza cuatro

Con tal fin, Ferrajoli analiza cuatro modelos de configuración posible de las diferencias: 1) indiferencia jurídica de las diferencias, 2) diferencia jurídica de las diferencias, 3) homologación jurídica de las diferencias y 4) igual valoración jurídica de las diferencias (Ferrajoli 2010). Este último modelo que defiende Ferrajoli se basa en el principio normativo de igualdad en los derechos fundamentales y al mismo tiempo “en un sistema de garantías capaces de asegurar su efectividad”. A diferencia del primero, este cuarto modelo garantiza Go 6976 todas su libre afirmación y desarrollo, no abandonándolas al libre juego de la ley del más fuerte, sino haciéndolas objeto de esas leyes de los más débiles que son los derechos fundamentales. Del segundo se distingue porque no privilegia ni discrimina ninguna diferencia, sino que las asume a todas como dotadas de igual valor. Del tercero lo separa el dato de que no desconoce las diferencias, sino que, por el contrario, reconoce todas y las valoriza como otros tantos rasgos de la identidad de las personas, sobre cuya concreción y especificidad cada una funda su amor propio y el sentido de autonomía en las relaciones con los demás.
Si algún derecho a la diferencia debe traducirse en un derecho desigual es el derecho a la maternidad voluntaria como autodeterminación de la mujer. Este derecho, afirma Ferrajoli con razón:
Termino con una última reflexión para evitar malos entendidos con respecto a esta defensa ferrajoliana del igual valor jurídico de las diferencias. Por ningún motivo se trata de defender una suerte de tolerancia hacia las diferencias; es decir, algo así como una resignación o indiferencia frente a aquello que nos distingue. ¿No resulta acaso ofensivo que alguien en un alarde de solidaridad se exprese diciendo que tolera las condiciones diferenciales de las mujeres en aras de una mejor convivencia social? ¡Hombre, muchas gracias por su deferencia! Por supuesto, resulta un paso importante para cualquier sociedad mínimamente decente superar la vocación discriminatoria y ejercer el hábito de la tolerancia, pero creo que aun este valor —tan querido para los liberales— debe entenderse de forma temporal: se debe trascender el límite impuesto por la tolerancia y aspirar hacia el estado de respeto. No el respeto bobo, sino aquel que se sustenta en el reconocimiento de las diferencias, así como en los principios de autonomía y dignidad humanas, valores en ningún sentido negociables.
La tolerancia sería un primer paso, una virtud transitoria, si se quiere, que debe dar lugar finalmente a la igual consideración y respeto de las personas en el contexto de una pluralidad diferenciada. Creo que esta es la idea de Ferrajoli que vale la pena destacar. En este sentido cito un pasaje ilustrativo de Goethe: “En realidad —decía Goethe—, la tolerancia no debería ser realmente más que un estado de espíritu pasajero, debiendo conducir al reconocimiento. Tolerar significa insultar”. Ernesto Garzón Valdés afirma que:

lo largo de las últimas décadas las teorías de género han tenido la extrema virtud de sostener desarrollos conceptuales que redundaron en la complejización de ciertos debates clave de la filosofía política. Su sofisticación teórica no solo ha sido capaz de enriquecer debates propios y desplegar justificaciones relevantes para sus programas políticos, sino que, además, ha impactado sobre otras áreas. Así, nombres como Nancy Fraser, Iris Marion Young, Martha Nussbaum o Judith Butler son protagonistas hoy de la escena filosófica gracias a, pero también más de allá de, los reclamos políticos que encabezan explícitamente.
Una de las tradiciones recientes que, aunque desarrollada en principio a Homogametic sex partir de una relación íntima con las disputas producidas al interior de las teorías de género, más ha impactado sobre la teoría política y social es, seguramente, el llamado “giro afectivo”. Aún cuando la denominación elegida pueda parecer un nuevo abuso de la mercadotecnia filosófica, lo cierto es que en la última década ha sido capaz de hacer ingresar en la discusión cuestiones que hasta entonces solo habían sido debatidas transversalmente o gracias al impacto lateral de la sociología de las emociones —de desarrollo algo anterior—. Leído en algunos casos como una suerte de respuesta al posestructuralismo () presente en el feminismo de la tercera ola, entendemos, tal como mostraremos aquí, que se trata más bien de una tendencia que, aunque crítica de ciertas lecturas de esa tradición, llega a profundizar algunas de las consecuencias del giro lingüístico tales como la inestabilidad y la contingencia. No se trata entonces de una perspectiva que busca invalidar el posestructualismo que tan fuertemente ha marcado la teoría de género y la teoría política en general, sino de llevar algunas de sus premisas hacia el terreno de lo corporal. Según argumentaremos, tomando como punto de partida objeciones puntuales a algunos de sus elementos, el giro afectivo en una de sus variantes lleva la matriz propia del giro lingüístico más allá del propio lenguaje pudiendo así evitar algunas de las objeciones que han sido vertidas sobre él tales como su reificación del lenguaje o su incapacidad para poder dar cuenta de la dimensión concreta de la política.