The sequences of the used primers are shown in Table 1. The amplification conditions were 95 °C for 5 min for initial denaturing, 40 cycles of 95 °C for 30 s for denaturing,

61 °C for 60 s for annealing and elongation. A melting curve was run afterwards. The difference in the cycle threshold (ΔCT) value was derived by subtracting the CT value for GAPDH, which served as an internal control, from the CT value for the target genes. All reactions were run in duplicates using a BioRad real time PCR machine (CFX 96 Real Time System). mRNA expression levels of target genes were expressed as a several fold increase according to the formula 2ΔCT (not exposed)–ΔCT (exposed). Preparation of cell extracts and immunoblotting: Cells were homogenized in 50 μl of lysis buffer (50 mM Tris, 150 mM NaCl, 15 mM EDTA, 0.1% Triton X-100 and 1 mM UK-371804 in vitro phenylmethylsulfonyl fluoride) incubated for 20 min on ice, centrifuged at 14,000 rpm for 5 min. Protein concentrations were determined with Thermo

Scientific BCA™ protein assay kit (Fish Scientific, Wohlen, Switzerland). Immunoblotting was performed as described. (Duong, F.H.; Filipowicz, M.; Tripodi, M.; La Monica, N.; Heim, M.H. Hepatitis C virus inhibits interferon signalling through up-regulation of protein phosphatase 2A. Gastroenterol. 2004, 126, 263–277.) To detect the PP2Ac and BiP band, the membranes were scanned with a Fujifilm FLA-9000 scanner (Bucher biotec, Basel, Switzerland). Membranes were stained after scanning with Ponceau S solution (Sigma–Aldrich, Buchs, Switzerland) to check for equal loading. ROS click here assay for assessment of reactive oxygen species (ROS) production: Huh7 cells were plated at a density of 50 000 cells per well in 96-well plates. O-methylated flavonoid After a 24 h recovery cells were treated with either toxic or non-toxic concentrations of

SiO2-NPs (0.005, 0.05 and 0.5 mg After 24 h incubation, the medium was aspirated and each well was washed with PBS. Thereafter, cells were incubated with 100 μM H2DCFDA for 30 min and washed again with PBS. H2DCFDA is a non-fluorescent, cell permeable substrate that is converted into a fluorescent product by reactive oxygen species. The fluorescence (extinction at 485 nm and emission at 530 nm) was measured by an automatic microplate reader (Tecan Infinite M200, Tecan, Männedorf, Switzerland). MTT assay for cytotoxicity assessment: Huh7 were plated at a density of 50 000 cells per well in 96-well plates. After 24 h, cells were treated with 0.005, 0.05 and 0.5 mg ml−1 SiO2-NPs for 24 h. Before adding 25 μL 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT, 5 mg mL − 1 in PBS, Sigma–Aldrich, Buchs, Switzerland) to each well, the medium containing the SiO2-NPs was soaked off, each well was washed once with PBS and 200 μL medium were added. Subsequently the plates were incubated at 37 °C for 3 h.

The alkaline phosphatase (ALP) activity of EMVs was assayed using ALP colorimetric

kit (AnaSpec, Fremont, CA). Briefly, 50-μg vesicles were incubated with a colorimetric substrate, para-nitrophenyl phosphate, and the conversion of para-nitrophenyl phosphate to p-nitrophenol on release of phosphate ions was monitored at 405 nm. The protein concentration of the EMV samples was measured by Bradford assay (Bio-Rad Laboratories, Hercules, CA). For detection of mCherry fluorescence on EMVs derived from mCherry-labeled, 143B luciferase–expressing, puromycin-resistant cells, EMV suspensions were examined microscopically using the Olympus (Center Valley, PA) IX71 inverted fluorescent microscope equipped with a xenon arc lamp and monochromatic complementary metal oxide semiconductor camera. In addition, flow cytometric Sirolimus solubility dmso www.selleckchem.com/products/ABT-888.html data were acquired on EMV suspensions using the BD LSR II flow cytometer integrated with FACSDiva software (BD Biosciences,

San Jose, CA, USA). For TEM, 143B EMV pellets were fixed in 2.5% glutaraldehyde, postfixed in 1% osmium tetraoxide (OsO4), dehydrated, embedded in epon resin, and cut into ultrathin sections. The sections were stained with uranyl acetate and lead acetate before mounting on EM grids. The sections were examined and photographed using a JEM 1400 electron microscope (JEOL USA, Inc., Peabody, MA, USA) (80 kV). To determine the biochemical composition of the 143B EMV cargo, Western blot analyses were performed according to the previously described method [30]. 143B EMVs

were homogenized in Tris lysis buffer (20 mM Tris, 137 mM NaCl, 1% Triton X-100, 10% glycerol, 1 mM PMSF, and 1 mM DTT). Crude lysates of 143B cells (12.5-25 μg) and EMVs (25-40 μg) were denatured in sodium dodecyl sulfate sample buffer, electrophoresed on 12% denaturing polyacrylamide gels, and visualized by Ponceau stain. For immunoblot analysis, the pheromone proteins from the gel were transferred on to a polyvinylidene fluoride (PVDF) membrane and incubated with the following primary antibodies: anti–MMP-1 and anti–MMP-13 (Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA); 200 μg/ml each) at 1:200, anti-CD-9 (SBI: System Biosciences (Mountain View, CA, USA); 0.25 mg/ml) at 1:1000, and anti-RANKL and anti–TGF-β (GeneTex (Irvine, CA, USA); 1 mg/ml) at 1:1000 dilution. Detection of the immunostained bands was done by ECL chemiluminescence detection system (Thermo Scientific, Rockford, IL). Image acquisition was done using LabWorks Image Acquisition and Analysis Software 4.6.00.0 (UVP Bioimaging Systems, Upland, CA) and Image Lab software for the ChemiDoc MP system (Bio-Rad Laboratories) at incremental exposure time frame of 15, 30, 60, 180, and 300 seconds.

31 presented a sensitivity of 59.1% and a specificity of 79.4% (Figure 1). As shown in Table 1, the relationship between preoperative peripheral blood NLR and clinical pathologic characteristics was investigated. One hundred thirty-five patients (52.73%) identified as high-NLR group had

an elevated NLR (> 2.31), and 121 patients (47.27%) were identified as low-NLR (≤ 2.31) group. Preoperative NLR level was closely correlated with the tumor size (range, > 5cm) (χ2 = 19.869; P < .001), clinical TNM stage (χ2 = 29.576; P < .001), PVTT (χ2 = 9.434; P = .002), distant metastasis (χ2 = 7.858; P = .005), and AST (χ2 = 4.779, P = .029). No obvious correlations with age, gender, HBsAg, AFP (> 20 ng/ml), and combination of liver cirrhosis and the number of tumors were observed (P > .05). Kaplan-Meier survival analysis showed that NLR > 2.31 was associated with a shorter DFS (Figure 2A) and OS ( Figure 2B). Univariate GSK-3 inhibitor analysis revealed that obvious association existed between clinical parameters and both DFS and OS ( Table 2). Mean DFS in patients with Quizartinib in vivo NLR ≤ 2.31 was 69.47 months (95% CI, 56.93-82.01) compared with 30.23 months (95% CI, 21.99-38.48) in patients with NLR > 2.31 (P < .001). Mean OS in NLR ≤ 2.31 group and NLR > 2.31 group was 76.15 months (63.35-88.96) and 37.96 months (28.52-47.40), respectively (P < .001). In addition to high-NLR

group (NLR > 2.31), size of tumor > 5cm, multiple tumor number, III-IV of TNM stage, and combination of PVTT, distant metastasis, and AST > 40 U/l were also associated with a shorter DFS and OS, and recurrence was associated with a shorter OS ( Table 2). As mentioned above, the cutoff value of NLR was selected as 3.0 [16] or 5.0 [17] and [18] in previous reports, so we also evaluated the patients with HCC in this study using these cutoff values. Kaplan-Meier survival analysis showed Niclosamide that NLR > 3.0 ( Figure 2, C and D) and 5.0 ( Figure 2, E and F) were associated with a shorter DFS and OS, but there are 81 (31.64%) cases with NLR > 3.0 in

256 patients with HCC ( Figure 2, C and D) and only 29 (11.33%) cases with NLR > 5.0 in 256 patients with HCC ( Figure 2, E and F). The Cox proportional hazards model was used to examine the association between clinicopathologic factors and DFS/OS after surgical resection of HCC (Table 3). After adjusting other confounding factors, except recurrence factor for OS, seven associated factors (high NLR, size of tumor > 5 cm, multiple tumor number, III-IV of TNM stage, and combination of PVTT, distant metastasis, and AST > 40 U/l) were analyzed for DFS and OS using the stepwise multivariate Cox proportional hazards model. Four factors were significant in the Cox proportional hazards model. The hazard ratio (HR), 95% CI, and P values of the four independent predictors are listed in Table 3. A stepwise multivariate Cox proportional hazards model revealed that high NLR (HR, 1.690; 95% CI, 1.247-2.291; P = .001), size of tumor > 5 cm (HR, 1.974; 95% CI, 1.200-3.

These studies have shown that jararhagin cleaves fibrinogen preferentially in A-α chains. The hydrolysis of fibrinogen 23 kDa fragment does not interfere in platelet aggregation response, but renders an abnormal fibrin polymerization by thrombin (Kamiguti et al., 1994b). Jararhagin also was able to degrade fibrin in a dose-dependent manner (Baldo et al., 2008). Another effect following interaction between jararhagin and plasma proteins is the enhancement of fibrinolysis due to increase in tissue-type plasminogen activator

activity and inactivation of α2-plasmin inhibitor (Sugiki et al., 1995). According to the authors, these effects occur only because the catalytic activity of jararhagin is unaffected Selleckchem Sirolimus by plasma proteinase inhibitors such

as α2-macroglobulin (Kamiguti et al., 1994a). Jararhagin interferes with platelet function by inhibition of collagen- and ristocetin-induced platelet aggregation (Kamiguti et al., 1996a). The inhibition of ristocetin-induced platelet aggregation by jararhagin occurs due to a catalytic effect of the toxin on vWF that hydrolyses the fragment enclosing the AI domain, ligand-site for the GPIb receptor (Kamiguti et al., 1996a). In opposition, jararhagin inhibits collagen-induced platelet aggregation by a multi-factorial mechanism, involving collagen and the α2β1 collagen-receptor, but not interfering with GPVI collagen-receptor Vincristine purchase (Kamiguti et al., 2000). The cleavage of β1 subunit of the α2β1 integrin by jararhagin was shown, interfering with the stability of α2 subunit that fails to interact with of native collagen via I domain (Kamiguti et al., 1996b). ADP ribosylation factor Moreover, the mechanisms involved in inhibition of platelet aggregation via collagen also include competition between jararhagin and collagen for the binding to α2β1-receptor (De-Luca et al., 1995; Kamiguti et al., 1996a). Specific binding of jararhagin to α2β1 integrin was reported (Moura-da-Silva et al., 2001) as well as its high affinity binding

to the generic triple-helices of type I and type IV collagens (Moura-da-Silva et al., 2008; Tanjoni et al., 2003a). The binding of jararhagin to both α2β1 integrin and collagen would compete with the binding between natural ligand and receptor, interfering with platelet activation. Indeed, in the presence of jararhagin, platelets stimulated with collagen present a reduced phosphorylation of the tyrosine kinase pp72 and FcR gamma-chain Syk phosphorylation (Kamiguti et al., 1997a, 1997b), disrupting the signal transduction induced by collagen. The result of jararhagin action on clotting factors and platelets would corroborate to the unclotable blood, reduction in platelet activity and consequent hemorrhagic lesions that follows B. jararaca envenomings ( Cardoso et al., 1993). Endothelial cells have also been investigated as potential targets for hemorrhagic toxins.

This is due mainly to three reasons: (1) the time step of calculation in high-resolution process-based models (the first type of model) is determined by the shortest time-scale process, i.e. usually of the order of seconds or minutes, and truncation errors generated after each calculation time step can accumulate during continuous run cycles in a long-term model, giving rise to substantial bias between the final simulation results and reality; (2) detailed time series of data (e.g. flows, waves and sediment) covering such a long time span serving as model boundary input are absent; and (3) the variation of Venetoclax clinical trial bathymetry occurring in a stochastically

short time period, e.g. in a wind storm period, may exceed the change in a longer time span (1 year). One way

of bridging the gap between the simulation of short-term hydrodynamics, sediment transport Dabrafenib purchase and morphological changes taking place over much longer timescales is to integrate the concepts of ‘reduction’ (de Vriend et al. 1993a,b, Latteaux 1995) and techniques of morphological update acceleration (Roelvink 2006, Jones et al. 2007) into high-resolution process-based models. Three approaches can be derived from the ‘reduction’ strategy: (1) model reduction, in which only the main driving terms on the scale of interest are considered, while small scale processes that can be smoothed over a longer time period are avoided or integrated into an average term; (2) input reduction, in which the input data many should be refined into some representative data groups capable of producing similar results as the whole variety of real time series on the scale

of interest; and (3) behaviour-based models, in which small scale processes are replaced by observational knowledge. By ‘extracting’ the most important processes responsible for the long-term coastal morphological evolution based on the concepts of ‘reduction’ and combining the technique of morphological update acceleration, high-resolution process-based models are applied to long-term simulation. Decadal tidal inlet change (Cayocca 2001, Dissanayake & Roelvink 2007), decadal micro-tidal spit-barrier development (Jiménez & Arcilla 2004), millennial tidal basin evolution (Dastgheib et al. 2008) and millennial delta evolution (Wu et al. 2006) were all simulated by such models, in which promising results were obtained. Recently, a modeling methodology was developed by the authors for simulating the decadal-to-centennial morphological evolution of wave-dominated barrier islands in the southern Baltic Sea (Zhang et al. 2010). The methodology consists of two main components: (1) a preliminary analysis of the key processes driving the morphological evolution of the study area based on statistical analysis of meteorological data and sensitivity studies, and (2) a multi-scale process-based morphodynamic model, in which the ‘reduction’ concepts and techniques for morphological update acceleration are implemented.

Hyperamylasemia

Protease Inhibitor Library related to lavage cytology occurred in 5 of 44 patients (11.4%), but pancreatitis developed in none of them, and we considered the risk related to the procedure acceptable because of its high sensitivity and specificity. The reason for this low morbidity could be the care taken during the procedure of lavage cytology; that is, 1 mL of saline solution was injected through the injection lumen while 1 mL of the fluid in the pancreatic duct was concomitantly aspirated via the aspiration lumen, thus avoiding an increase in intrapancreatic ductal pressure. It would have been more difficult to aspirate a sufficient volume of mucous pancreatic juice using other commercially available double-lumen catheters because of the thin cross-sectional area of their aspiration lumen. The cross-sectional area of aspiration lumen of our double-lumen cytology catheter

is large because of the coaxial structure of the INCB024360 chemical structure catheter and mucous pancreatic juice could be easily aspirated at a rate of 30 mL per 1 or 2 minutes. As a result, mucin staining of the aspirated material was feasible in all our resected cases. The diagnostic efficacy of smear cytology may vary depending on the level of proficiency of the cytopathologists even if a sufficient number of cells are sampled.7, 20 and 21 On the other hand, the cell block method allows cytological and/or histological evaluation with H&E staining, which is familiar to pathologists.8 Actually, the present study showed a sensitivity of 92% and a specificity of 100% with H&E staining; besides, even the neoplastic epithelium of IPMNs could be examined in each cell block section. Nevertheless, discrepancy during pathological assessment of IPMNs is a clinical issue that needs to be resolved. Although histology was evaluated by experienced pathologists in the present study, a multicenter prospective analysis based on a more objective rule will be required so that it can be assessed even by less experienced pathologists in the near future.22 Furthermore,

the cell block method allows MUCs 1, 2, 5AC, and 6, which are essential to determine the histological subtype of IPMNs; namely, intestinal, gastric foveolar, oncocytic, aminophylline and pancreatobiliary.9, 10 and 11 Subclassification of IPMNs could be useful for the evaluation of the malignant potential of IPMNs.9, 10, 11 and 23 Most intestinal-type IPMNs express MUC2 and MUC5AC but not MUC1 and are thought to progress to invasive mucinous carcinoma, which has a better prognosis compared with pancreatobiliary and oncocytic IPMNs, which are positive for MUC1 and MUC5AC but negative for MUC2 and thought to progress to invasive tubular adenocarcinoma. Most gastric foveolar–type IPMNs express MUC5AC but not MUC1 or MUC2 and have been found to be noninvasive.

The 131Xe isotope (32.8 MHz resonance frequency at 9.4 T, 21.2% natural abundance) has a spin I = 3/2 and thus possesses a nuclear electric quadrupole moment (Q = −11.4 fm2) [16]. The electric quadrupole moment of the 131Xe nucleus is susceptible to interactions with electric field gradients (EFGs) and therefore serves as a sensitive probe for environmentally induced distortions of its large surrounding electron cloud [14]. Unless high concentrations of paramagnetic substances are present, these quadrupolar interactions are the dominant cause of 131Xe nuclear spin relaxation in all phases. Further, 131Xe coherent quadrupolar interactions can be induced when the www.selleckchem.com/products/AG-014699.html xenon atoms are contained within an anisotropic environment.

In solid, natural abundance xenon, Warren

and Norberg [17] and [18] found that 131Xe had a very short longitudinal relaxation time of T1 ≈ 200 ms at temperatures close to the melting point (161 K). However, the T1 increased monotonically by more than three orders of magnitude with decreasing temperature and reached T1 = 390 s at 9 K. The relaxation times in liquid xenon show the opposite trend compared to the solid and increase from T1 ≈ 40 ms at 161 K to T1 ≈ 80 ms at 250 K and 3 MPa. Later work [19] determined T1 = 110 ms at conditions just below the critical point, i.e. 298 K and 5.8 MPa. The 131Xe relaxation behavior of xenon dissolved PD-166866 mouse in various solvents was subject to experimental and computational studies in the past (see [20] for a review). Longitudinal relaxation in polar solvents is quite fast (T1 < 10 ms) due to the electric field gradient fluctuations induced by the solvent molecule dipoles. Even in non-polar solvents, the 131Xe T1 relaxation times are typically below 50 ms. In gas phase, it was theoretically predicted by Staub and later confirmed experimentally by Brinkmann

et al. [21] that the 131Xe longitudinal relaxation time (T  1) is inversely proportional to the gas density, ρ  , with equation(1) 1/T1131Xe=ρ·3.96×10-2amagat-1s-1.1 amagat is the density of the specific gas at standard pressure and temperature of 101.325 kPa and 273.15 K. For xenon the atomic number density of one amagat is reported with 2.7048 × 1025 m−3 [22]. (Note that in literature the cAMP amagat is often alternatively defined as the density of an ideal gas at standard pressure and temperature resulting to the slightly different value of 2.6868 × 1025 m−3.) Brinkmann’s result was obtained at a temperature of 298 K and 0.76 T magnetic field strength. In later theoretical work, Adrian [23], considered separately the relaxation dependence on van der Waals and exchange contributions during binary collisions. He obtained 1/T1131Xe=ρ·4.61×10-2amagat-1s-1 for the gas at room temperature but also noted a temperature dependence of the 131Xe relaxation. From these equations, a 131Xe gas-phase relaxation time of T1 ≈ 22–25 s would be expected at ambient pressure (∼1 amagat).

Diagnostic imaging plays a central role in ARM evaluation. Because of the lack of ionizing radiation, excellent intrinsic contrast resolution, multiplanar imaging capabilities, technical advances in hardware, and innovative imaging protocols, magnetic resonance (MR) imaging is increasingly important in assessment of ARM patients in utero, postnatally before definitive surgical selleck chemicals correction, and in the postoperative period. This article discusses the role of MR imaging in evaluating ARM patients. Matthew R. Hammer, Jonathan R. Dillman, Ethan A. Smith, and Mahmoud

M. Al-Hawary Noninvasive, nonionizing, multiparametric magnetic resonance (MR) imaging of the pelvis using a field strength of 3-T now provides a comprehensive assessment of perineal involvement in pediatric Crohn disease. MR imaging accurately evaluates inflammatory disease activity, and allows determination of the number and course of fistula tracts as well as their relationships PFT�� ic50 to vital perianal structures, including the external anal sphincter, helping to guide surgical management and improve outcomes. This article provides an up-to-date review of perineal MR imaging findings of Crohn disease in the pediatric population, including fistulous disease, abscesses, and skin manifestations.

Imaging technique is also discussed. Ethan A. Smith Advances in the treatment of pediatric abdominopelvic malignancies have increased survival drastically. Imaging is critical in initial tumor characterization/staging, assessment of treatment response, and surveillance following therapy. Magnetic resonance imaging (MRI) is playing an increasing role in the care of these patients due to its lack of ionizing radiation, superior contrast resolution and the ability to characterize tumors based on tissue characteristics (e.g., Selleckchem Paclitaxel T1 and T2 relaxation times). Modern MR techniques also allow for assessment of tumors based on functional characteristics. This

article is focused on emerging MRI technologies and potential applications in the imaging of pediatric abdominopelvic malignancies. Ranjith Vellody, Peter S. Liu, and David M. Sada Although traditional catheter-based angiography has been the gold standard for pediatric abdominal and pelvic vascular imaging for the past several decades, advances in magnetic resonance angiography (MRA) have made it a viable alternative. MRA offers several advantages in that it is noninvasive, can be performed without ionizing radiation, and does not necessarily rely on contrast administration. The ability of modern MRA techniques to define variant vascular anatomy and detect vascular disease may obviate traditional angiography in some patients. Index 861 “
“Current Opinion in Chemical Biology 2013, 17:506–514 This review comes from a themed issue on Energy Edited by Michael D Burkart and Stephen P Mayfield For a complete overview see the Issue and the Editorial Available online 26th March 2013 1367-5931/$ – see front matter, © 2013 Elsevier Ltd. All rights reserved. http://dx.

, 1994). After its transportation, LPC is rapidly converted into different products by specific routes which are important to regulate LPC levels on such tissues (Illingworth and Portman, 1972). However, the real content and the presence of LPC in cells or tissues are difficult to accurately determine (Schilling et al., 2004).

But, in vitro experiments showed that values above 50 μM, LPC is considered toxic, since plasma membrane integrity is disturbed due to its detergent-like feature ( Masamune et al., 2001). In fact, LPC is an intriguing molecule and should be more investigated. Data from literature point out the participation of PKC pathway in the retina ganglion cells leading them to survive (Santos and Araujo, 2000 and de Rezende Corrêa et al., 2005). PKC enzymes have been the primary mechanisms implicated in several biological effects, but the molecular basis for such activation Protein Tyrosine Kinase inhibitor is poorly understood. So, the increased survival Epigenetic inhibitor cost of retinal ganglion cells induced by LM-PLA2-I as well as LPC showed to be dependent of PKC pathway since this effect was abolished in the presence of a PKC inhibitor (chelerythrine chloride). PKC comprises a family of serine/threonine kinases involved in different events of neuronal development, as proliferation, survival and apoptosis (Wooten, 1999). This family is divided into three groups; the conventional one (α, β,

γ) depends on calcium ion and is activated by diacylglycerol and phorbol ester; the atypical (ζ, λ) is calcium independent and is not activated by diacylglycerol or phorbol ester

while the novel class (δ, ɛ, η, θ) is also calcium independent, but it is activated by diacylglycerol or phorbol ester (Michie and Nakagawa, 2005 and Reyland, 2009). To evaluate the participation of classical PKC isoforms and calcium, BAPTA-AM was employed. As seen, the survival effect induced by LM-PLA2-I was not affected in the presence of BAPTA-AM. Thus, discarding the involvement of such group and the need of increase intracellular calcium levels on this trophic effect. These results, in part, are in contrast to Rigoni et al. (2007) and Montecucco and Rosseto (2008). They observed that the neurotoxic effect exhibited by taipoxin (a potent snake PLA2 neurotoxin isolated from Oxyuranus scutellatus) was dependent on the increase on intracellular calcium levels. However, we would like to emphasize Parvulin that our data are quite different from these authors’ results; because taipoxin displayed toxic effects on neurons and LM-PLA2-I had trophic or protective effects on neuronal ganglion cells. Rottlerin (a PKCδ isoform inhibitor) abolished the LM-PLA2-I-induced survival. However, rottlerin is not enough to state that the LPC-induced survival upon ganglion cells occurs through PKCδ pathway, but we might infer or postulate that this finding indicates a possible involvement of such enzyme to enhance on LPC-induced retinal ganglion survival effect.

, 2002); 1s44:A (26% identity; apocrustacyanin) (Habash et al., 2004), 3ebw:A (26% identity; cockroach allergen) (Tan et al., 2008). The 3D molecular model of each peptide, including pM2c, was built up Bioactive Compound Library cell line considering the seven amino acid sequence extracted from the 3D molecular structure (NMR, X-ray diffraction, and homology) of each related protein previously selected (Discovery Studio v3.1.1; Accelrys Software Inc., 2005–2011) (see Fig. 3), and constrains were made to maintain the conformational arrangement of each peptide sequence during calculation. The three last characters of PDB ID were used to name those peptides. The molecular models were

parameterized using Amber99 force field (Wang et al., 2000), and partial atomic charges were calculated employing the AM1 semiempirical method (Dewar et al., 1985) (HyperChem 8.0 for Windows; Hypercube, Inc., 1995–2009). Then, forty-nine molecular properties or descriptors of different nature were computed using the appropriate software package (Gaussian 03W, Gaussian, Inc., 2003; Marvin 5.10.3, ChemAxon Ltd., 1998–2012; HyperChem 8.0 find more for Windows; Hypercube, Inc., 1995–2009; Discovery Studio v3.1.1; Accelrys Software Inc., 2005–2011). Those properties are related to the following contributions: (1) electronic [Hartree-Fock/3-21G* method: dipole moment (μ), partial atomic electrostatic charges (CHELPG or ESP), maps of electrostatic

potential (MEPs), frontier molecular orbital energies (EHOMO, ELUMO, gap = EHOMO − ELUMO), polarizability (α)]; (2) hydrophobic [calculated n-octanol/water partition coefficient (ClogP) of nonionic species, ClopD at the isoelectric point, maps of lipophilic potential (MLPs)]; (3) apparent partition [ClogD at pH 1.5, 5.0, 6.0, and 7.0]; (4) steric/hydrophobic [molar refractivity (MR)]; (5) steric/intrinsic [van der Walls volume (VvdW), solvent accessible volume (Vsolv)]; and (6) geometric [polar surface area (PSA), molecular surface area (MSA or SAvdW), solvent accessible surface area (ASA or SASA), ASA+ (atoms with positive charges), ASA− (atoms with negative charges),

ASA_H (hydrophobic atoms), ASA_P (polar atoms)]. After a previous variables or descriptors selection, a table (or matrix X) containing eleven rows, which correspond to the samples (peptides), FER and twenty-seven columns, which correspond to the descriptors (molecular properties) (Supplementary information section), was used as input for the exploratory data analysis. Due to the distinct magnitude orders among the calculated variables, the autoscaling procedure was applied as a preprocessing method (Ferreira et al., 1999). The exploratory analysis was carried out employing the Pirouette 3.11 software (Infometrix, Inc., 1990–2003). PCA is a data compression method based upon the correlation among variables or descriptors.