291, P < 0.01; Friedman test), opposed to non-significant changes of neopterin in women with unsuccessful treatment (chi-squared = 8.203). The steady increase of neopterin concentrations upon blastocyst transfer indicates that heightened production of neopterin in

very early phases of pregnancy Compound C chemical structure may serve as an early predictor of successfully progressing pregnancies in humans. (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.”
“Objective: To determine the relationship of biomarkers of placental damage by oxidative stress in pre-eclamptic placenta. Methods: A case-control study was performed on a population of 14 pregnant women with PE and 12 women with normal pregnancies. Immunohistochemical expressions of VEGF, vWF distribution, (Na + K)-ATPase activity, and abundance of nitrotyrosine residues, were assessed in the placental tissue. Results: Women with pre-eclampsia showed increased VEGF expression

and abundance of nitrotyrosine residues in placental villous, and plasma vWF levels (p < 0.05), whereas placental (Na + K)-ATPase activity were significantly reduced. The syncytiotrophoblast and the maternal space of pre-eclamptic placenta showed diminished and increased vWF expression, respectively, but no significant differences in its expression were found in the placental endothelium and stroma (p < 0.05). Conclusions: It could be suggested that increased oxidative MRT67307 order stress IGF-1R inhibitor and VEGF contribute to enhance the impairment of placental perfusion by increasing peroxynitrite formation, product of the NO and superoxide reaction, thereby partly contributing to account for the pathophysiology of this disease. The presence of vWF in the maternal space and its diminished expression in syncytiotrophoblast of pre-eclamptic placenta also might have pathogenic implications.”
“Preliminary studies have shown that systemic beta-human chorionic gonadotrophin (beta HCG) therapy alleviates endometriosis-related chronic pelvic pain. The underlying mechanism,

however, is completely unknown. This study has investigated the dose-dependent alterations in the overall gene expression profile of endometriosis-derived stromal cells under increasing concentrations of beta HCG by using the Affymetrix Gene Chip U133 Set. It has been previously shown that beta HCG concentrations of 0.1 U/ml and higher lead to a significant and dose-dependent increase in the expression of 68 genes. This study reports on a cluster analysis which identified three clusters of genes with a comparable expression pattern in response to increasing concentrations of beta HCG. Most of the up-regulated genes encoded proteins that are involved in cell adhesion, intercellular communication, extracellular matrix remodelling, apoptosis and inflammation.

Meanwhile, the mechanism underlying the role of BMMF see more on active sites

is revealed (i) convert atactic sites (I) to weakly isospecific site (II) by occupying either or both of L-1 or/and L-2 vacancies around site; (ii) improve the isotacticity of weakly isospecific site (II) in donor-free ZN catalyst by adsorbing at L-2 vacancy or/and replacing the Cl for TiCl4 at L-1; and (iii) replace highly isospecific site (III). In addition, these roles of BMMF are successively achieved according to the amount of BMMF added. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012″
“In the Tokat and Sivas provinces of Turkey, the overall Crimean-Congo hemorrhagic fever virus (CCHFV) seroprevalence was 12.8% among 782 members of a high-risk population. CCHFV seroprevalence was associated with history of tick bite or tick removal from animals, employment in animal husbandry or farming, check details and being > 40 years of age.”
“An electronic survey assessing primary care pediatricians’ estimations and practices regarding parents’ vaccination refusal was sent to 395 members of the European Academy of Pediatrics Research in Ambulatory Setting network, with a response rate of 87%. Of respondents who vaccinate

in the clinic, 93% estimated the total vaccine refusal rate as <1%. Of all respondents, 69% prefer a shared decision-making approach to handle refusing parents.”
“Abnormal anti-Stokes Raman emission (AASRE) is defined by an anti-Stokes/Stokes intensity ratio much greater than expected on the basis of the equilibrium population of excited vibration states provided by the Boltzmann law. Using nonlinear optical materials such as LiNbO(3) and CdS in powder form, we demonstrate that under continuous single beam excitation it presents AASRE

Protein Tyrosine Kinase inhibitor whose properties are similar to a single beam pumped Coherent Anti-Stokes Raman Scattering. We explain AASRE as resulting from a wave-mixing mechanism of the incident laser light with a Stokes shifted Raman light produced by a spontaneous Raman light scattering process, both strongly scattered inside the sample. (C) 2011 American Institute of Physics. [doi:10.1063/1.3633936]“
“Long-chain branched poly(butylene succinate) were synthesized through a two-step process of esterification and polycondensation, using 1,2,4-butanetriol (1,2,4-BT) as a long-chain branching agent. The effect of long-chain branches on the crystallization behaviors, rheological properties, and tensile properties was investigated systematically.

Interventions: Both awake and drug induced sleep endoscopy were performed. Endoscopy video recordings were mixed at random on a DVD. Two pediatric otolaryngologists and two pediatric pulmonologists independently scored each recording using an upper airway endoscopy scoring survey. Main outcome measures: reviewers scored the following parameters: each structure’s contribution (nose, nasopharynx, lateral pharyngeal walls, tongue base, supraglottis) to the obstruction, the AS1842856 manufacturer main site in which the obstruction occurs, the severity of OSA (mild, moderate,

severe), the level of confidence of endoscopy findings (poor, fair, good).

Results: When reviewing sleep endoscopy recordings for the upper airway obstruction site, the highest correlation among the four observers was found for the nasopharynx and the supraglottis (Kappa SBE-β-CD order score: 0.6 and 0.5, respectively). Compared to awake endoscopy, sleep endoscopy demonstrated more cases of airway obstruction caused by collapse

of lateral pharyngeal walls and base of tongue (McNemar test for symmetry, P value < 0.05). Level of confidence among the four observers was higher in older children and lower in children with severe OSA.

Conclusions: Sleep endoscopy is a consistently reliable tool for identifying the site of obstruction in children with persistent OSA. Though anesthetic induced sleep is not a perfect model for real sleep, the technique demonstrably guides further therapy better than awake endoscopy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“A rapid, sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the determination of propiverine hydrochloride (CAS 54556-98-8) in human plasma using cetirizine di-hydrochloride as internal standard Volasertib manufacturer (IS, CAS 8388-51-0). Following liquid-liquid extraction with ethyl acetate, the separation was performed on a reverse phase C(18) column with a mobile phase consisted of methanol-ammonium acetate (pH 4.0; 10 mM) (70:30,

v/v). The detection was performed by a triple-quadrupole mass spectrometer in the positive ion and multiple reaction monitoring (MRM) mode, m/z 368.3 -> 116.1 for propiverine and m/z 389.2 -> 201.0 for the IS. The calibration curve fitted well over the concentration range of 0.2-200 ng/mL (all the concentration data in this study are related to salt (propiverine hydrochloride)). The limit of detection (LOD) and lower limit of quantification (LLOQ) in human plasma were 0.05 and 0.2 ng/mL, respectively. The method was proved to be rapid, sensitive, specific, accurate and reproducible and has been successfully applied to a pharmacokinetic study of propiverine hydrochloride sustained release capsules (the 30 mg dose in this”
“Aims: Acute otitis media (AOM) is one of the most frequent diagnoses and reasons for prescribing antibiotics in children.

Ten OC pesticides (beta-hexachlorocyclohexane, hexachlorobenzene, heptachlor epoxide, p,p’-DDE, p,p’-DDD, p,p’-DDT, o,p’-DDT, oxychlordane, trans-nonachlor, and mirex) detectable in >= 70% of controls were analyzed in relation to diabetes. Most OC pesticides showed strong associations with type 2 diabetes after adjusting for age, sex, BMI, alcohol consumption, and cigarette smoking. Compared with subjects in the lowest tertile of each OC pesticide, adjusted odds ratios (ORS) in the 3rd tertile ranged from 3.1 (95% CI 0.8-12.1) for heptachlor epoxide to 26.0(95% MX69 purchase CI

1.3-517.4) for oxychlordane. In the case of chemicals belonging to the DDT family, adjusted ORs in the 3rd tertile were in the range of 10.6 (95% CI 1.3-84.9) for pp-DOT to 12.7 (95% CI 1.9-83.7) for p,p’-DDE.

In this exploratory study with small sample, low-dose background exposure to OC pesticides was strongly associated with prevalent type 2 diabetes in Koreans even though absolute concentrations of DC pesticides were no higher than in other populations. Asians may be more susceptible to adverse effects of OC pesticides than other races. (C) 2010 Elsevier Ltd. All rights reserved.”
“Objective: To confirm the role of fetal growth restriction (FGR) as a cause of stillbirth, and to compare diagnostic accuracy of customized learn more fetal growth and population-based standards in identifying FGR within a pathological population of early and late stillbirths. Methods: Retrospective study on a cohort of 189 stillbirths occurred in single pregnancy between January 2006 and September 2011. Unexplained stillbirths, defined by Aberdeen-Wigglesworth and ReCoDe classifications,

were evaluated on the basis of fetal birthweight Bafilomycin A1 mw with both Tuscany population and Gardosi customized standards. Unexplained stillbirths have been classified as early or late depending on the gestational age of occurrence. Results: Aberdeen-Wigglesworth classification, applied to the 189 cases of stillbirth, left 94 unexplained cases (49.7%), whereas the ReCoDe classification left only 40 (21%). By applying population standards to the 94 unexplained stillbirths we have identified 31 FGRs (33% of sample), while customized standards identified 54 FGRs (57%). Customised standards identified a larger number of FGRs with respect to population standards during the third trimester (i.e. 51% vs. 25% respectively) than in the second trimester (73% vs. 54% respectively) (p = 0.05). Conclusions: Customized standards have a higher diagnostic accuracy in identifying FGRs especially during the third trimester.”
“Pooled yellow eel (Anguilla anguilla L) samples, consisting of 3-10 eels, from 50 locations collected in the period 2000-2006 were used to assess the pollution with PBDEs and HBCDs in Flemish waters (Belgium).

Safety of the procedure was reported. Results: The study included 8 male and 7 female patients with a mean age of 33.3 +/- 20.3 years (range 7-65). Biopsy was carried out under computed tomography and ultrasound https://www.selleckchem.com/products/jnk-in-8.html guidance in 12 and 3 patients, respectively. There were 2 nonrepresentative biopsies that were proved to be adrenocortical carcinoma and myelolipoma after adrenalectomy. Results of biopsy in the remaining 13 patients provided accurate diagnosis as proved

by definitive histopathology in all but 2 in whom the final diagnosis was established as adrenocortical carcinoma while biopsy was paraganglioma in one and cortical adenoma in the other. Overall sensitivity and negative predictive value of adrenal biopsy was 73.3 and 60%, respectively. Apart from two mild hypertensive episodes following silent pheochromocytoma biopsy, no complications were reported. Conclusions: Percutaneous biopsy is a safe procedure for the diagnosis of pathologic conditions of the adrenal gland

with a reasonable diagnostic aid. Copyright (C) 2010 S. Karger AG, Basel”
“In nature, no single plant completes its life cycle without encountering environmental stress. When plant cells surpass stress threshold stimuli, chemically reactive oxygen species (ROS) are generated that can cause oxidative damage or act as signals. Plants have developed numerous ROS-scavenging systems to minimize the cytotoxic effects Tariquidar of ROS. The role of sucrosyl find more oligosaccharides (SOS), including fructans and the raffinose family oligosaccharides (RFOs), is well established during stress physiology. They are believed to act as important membrane protectors in planta. So far a putative

role for sucrose and SOS during oxidative stress has largely been neglected, as has the contribution of the vacuolar compartment. Recent studies suggest a link between SOS and oxidative defence and/or scavenging. SOS might be involved in stabilizing membrane-associated peroxidases and NADPH oxidases, and SOS-derived radicals might fulfil an intermediate role in oxido-reduction reactions taking place in the vicinity of membranes. Here, these emerging features are discussed and perspectives for future research are provided.”
“Ischemic stroke is a major cause of morbidity and mortality for which the only approved treatment in the acute setting is intravenous thrombolysis. The efficacy and safety of recombinant tissue plasminogen activator (rt-PA) have been firmly established within 3 h of symptom onset; however, few patients are eligible for treatment in this time window. Expanding the time for treatment has been challenging, but new evidence has demonstrated a modest statistical improvement in selected patients when rt-PA is administered within 4.5 h.

05). In warm obturation technique, no significant difference was found Crenolanib mouse between the 2 groups ( with and without the smear layer) of AH26 (P > .05). On the contrary, in groups of Pulp Canal sealer, fluid transport values were significantly less when the smear layer was removed (P > .05). Finally, no significant difference was observed between the groups of Gutta-Flow (with and without the smear layer) (P >

.05).

Conclusions. Under these in vitro conditions, it seems that smear layer removal improves the ability of the filling materials to prevent the fluid movement, at least after the use of warm obturation techniques. On the contrary, smear layer removal does not seem to improve the same ability after the use of cold lateral compaction technique. Further laboratory and also clinical studies are needed in the future to compose a clear view concerning the improvement of sealing ability following smear layer removal. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:e145-e153)”
“A series of environmentally friendly waterborne poly(urethane acrylate) (WPUA)/silica (SiO(2)) hybrids were synthesized by a sol-gel process on the basis of isophorone diisocyanate, polyester polyol (GE-210),

dimethylpropionic acid, butyl acrylate and methyl methacrylate monomers, tetraethoxysilane (TEOS), and 3-glycidyloxy-propyl trimethoxysilane (GLYMO) Selleckchem Erastin as a coupling agent. The mechanical properties of the WPUA/SiO(2) hybrids were investigated through tensile and hardness tests. Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, https://www.selleckchem.com/products/cl-amidine.html atomic force microscopy, and X-ray diffraction were used to assess the fracture surface morphology and the dispersions of the WPUA/SiO(2) hybrids. The strength and hardness values of the WPUA/SiO(2) hybrids were improved significantly. This was attributed to the synergistic effect

of WPUA, GLYMO, and TEOS. The results show that SiO(2) particles of the membranes had a uniform dispersion and formed an excellent interfacial bonding layer on their surfaces. The prepared hybrids showed good thermal stability and mechanical properties in comparison with pure WPUA and showed tunable transparence with the SiO(2) fraction in the film. Through suitable adjustment of the TEOS content, some thin hybrids have potential applications as specialty materials. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 1683-1695, 2011″
“Study Design. This is a case report of a posterior extrusion of the polyethylene core from a CHARITE arthroplasty. This is the first reported case of posterior dislocation of the polyethylene and the revision strategies used to correct this problem.

Objective. To report a novel failure mechanism and revision strategy for CHARITE total disc arthroplasty (TDA).

The refractive index (n) and thermo-optic coefficient (dn/dT) of the CAPU were measured at 650 nm wavelength and different temperature by attenuated total reflection (ATR) technique. By using CCD digital imaging devices, transmission loss of CAPU was measured and the value

is 0.565dB/cm. The results will provide the foundation for many potential applications such as digital thermo-optic switch materials and other fields in the future. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 2567-2572, 2011″
“BiFeO(3) (BFO) and 4 wt. % Al-doped ZnO (ZAO) layers were grown on indium tin oxide (ITO) glass substrate using a pulsed laser deposition (PLD) method. I-V curves of Selleck LY2835219 the ZAO/BFO/ITO glass structure were investigated over the temperature range from 60 to 240 K. Analysis of the leakage current demonstrates that Poole-Frenkel emission is the dominant mechanism in our sample. The relations between resistance and temperature at positive and negative bias voltages are different, and the difference arises from the ferroelectric switching in BFO and the interfacial depletion layer between Stem Cell Compound Library research buy the semiconducting and the ferroelectric layers. Magnetoresistance (MR) effect is observed and the negative MR is related to the electron spin-dependent scattering and the interface resistance of the heterostructure. (C) 2011 American Institute of Physics. [doi:10.1063/1.3567304]“
“A

biologically active diacid monomer, 5-(2-phthalimidoethanesulfonamido) isophthalic acid (6), based on taurine, was easily prepared in three steps. Also a series of novel biologically active polyesters (PE)s were synthesized by the reaction of this monomer with several aromatic diols by step growth polymerization using tosyl chloride (TsCl)/dimethylformamide (DMF)/pyridine (Py) system as a condensing agent. The resulting new polymers were obtained in good to high yields with moderate inherent viscosities. All of the PEs were

characterized by FTIR and some of them were also characterized by H-1-NMR and elemental analyses methods. The thermal stability of PEs was evaluated with thermogravimetric analysis and differential scanning calorimetry techniques under a nitrogen atmosphere and it was found that they have moderate stability. Wheat seedlings were normally grown in KPT-8602 cost the presence of 6 and it’s derived PEs in soil. Also the high dehydrogenase activities in treated soils with obtained compounds showed biodegradability of polymers under soil burial in natural environments. It can be concluded that the synthesized compounds derived from taurine are possibly biologically active and environmentally nontoxic for soil microorganisms. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 2573-2583, 2011″
“In this study, the magnetic properties of CoFeSiB glass covered amorphous wires (GCAWs) concerning their anisotropy, susceptibility, and coercivity have been investigated.

Under the optimized conditions, a calibration plot for SAL was obtained with a linear range between 0.08 ng/mL and 1000 ng/mL (r = 0.9955). The detection limit was 0.04 ng/mL. The immunosensor was examined in real feed and pork samples for the analysis of SAL (C) 2010 Elsevier Ltd.

All rights reserved.”
“Data of 11 infants (median gestational age and birth weight 30 weeks and 1520 g, respectively) with severe human rhinovirus infection (HRV) are described. Nine of 11 (82%) were preterm infants and 7 of these 9 (78%) became infected during their stay Selleckchem PU-H71 in the neonatal intensive care unit. All infants presented with respiratory distress and all needed respiratory support for a median of 6 days. Radiologic findings included perihilar streakiness, atelectasis, focal consolidation, and hyperinflation. The diagnosis of HRV infection was made by real- time polymerase chain reaction in nasopharyngeal aspirate. All infants recovered from their HRV infection. HRV can cause severe disease in preterm infants requiring respiratory support.”
“Chemoprevention by dietary constituents in the form of functional food has emerged as a novel approach to control inflammatory diseases and cancers. Recently we reported for the first time that iron content is a critical

determinant in the anti-tumour activity of bovine milk lactoferrin (bLf). We therefore wanted to evaluate the chemo-preventative efficacy of Apo-bLF and 100% LDN-193189 datasheet iron-saturated bLF (Fe-bLF) on hydrogen peroxide (H2O2)-induced colon carcinogenesis, and their influence on antioxidant enzyme activities within Y-27632 purchase colon carcinogenesis. This was undertaken through observing how oxidative stress induced by H2O2 alters antioxidant enzyme activity within HT29 colon cancer cells, and then observing changes in this activity by treatments with the different antioxidants ascorbic acid (AA), Apo-bLF and Fe-bLF. All antioxidant enzymes

(catalase, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GsT) and superoxide dismutase (SOD)) appeared to be increased within HT29 cells, even prior to H2O2 exposure, and all enzymes showed significant decreased activity when cells were treated with the antioxidants AA, Apo-bLF or Fe-bLF, with or without H2O2 exposure. The results indicate that all three antioxidants have the ability to scavenge ROS, lower antioxidant enzyme activities within already excited states, and possibly allow colon cancer cells to be overcome by oxidative stress that would normally be prevented, perhaps leading to damage and potential apoptosis of the cancer cells. In conclusion, the anti-oxidative effects of Apo-bLF and Fe-bLf studied for the first time, show dynamic changes that may allow for necessary protection from imbalanced oxidative conditions, and potential at reducing the ability of cancer cells to protect themselves from oxidative stress states.

In agar diffusion method, the 95% ethanol extracts

from 12 of the algae showed growth inhibition against the tested microorganisms. In particular, Ishige okamurai, Ecklonia stolonifera, Sargassum siliquastrum, Sargassum thunbergii, Colpomenia bullosa, and Ecklonia cava had strong antibacterial activities against Gram-positive WH-4-023 cost bacteria at 4 mg/mL. In the results of the MIC test, S. siliquastrum showed the most antimicrobial activity, where its MIC values ranged from 0.005 to 0.0075% against Listeria monocytogenes, Clostridium perfringens, and Basillus subtilis. In the thermal stability test, fro the ethanol extracts of I. okamurai. E. cava. S. siliquastrum, S. thunbergii, and C. bullosa. the extracts proved to maintain high antimicrobial activities when they were treated at 121 degrees C for 15 min. In the pH stability test, the antimicrobial activity of the S. siliquastrum ethanol extract was stable from pH 2 to 10, whereas the activity of the other species ethanol extracts were weakend under pH 10 against several microbes.”
“Ghrelin is a brain-gut peptide that was discovered through reverse pharmacology and was first isolated from extracts of porcine stomach. Ghrelin binds to growth hormone secretagogue receptor (GHS-R)

and is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT). Several important biological functions of ghrelin have been identified, which include its growth hormone-releasing Selleck CA4P and appetite-inducing effects.

Ghrelin exerts its central orexigenic effect mainly by acting on the hypothalamic arcuate nucleus via the activation of the GHS-R. Peripherally ghrelin has multiple metabolic effects which include promoting gluconeogenesis P5091 datasheet and fat deposition. These effects together with the increased food intake lead to an overall body weight gain. AMP-activated protein kinase, which is a key enzyme in energy homeostasis, has been shown to mediate the central and peripheral metabolic effects of ghrelin. The hypothalamic fatty acid pathway, hypothalamic mitochondrial respiration and uncoupling protein 2 have all been shown to act as the downstream targets of AMPK in mediating the orexigenic effects of ghrelin. Abnormal levels of ghrelin are associated with several metabolic conditions such as obesity, type 2 diabetes, Prader-Willi syndrome and anorexia nervosa. The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment.”
“Aims: The purpose of this scoping review was to examine research activity comparing suprapubic catheterization to any other method of chronic bladder emptying such as intermittent and indwelling catheterization in adults in relation to complications, patient satisfaction, and health-related quality of life (QoL).

(c) 2011 American Institute of Physics. [doi:10.1063/1.3600203]“
“The receptors for the immunosuppression drugs FK506 and rapamycin are called FKBPs (FK506-binding proteins). FKBPs comprise a large family; they are found in many species, including bacteria, fungi, animals, and plants. As a class of peptidyl-prolyl cistrans isomerase enzymes, the FKBP genes

have been the focus of recent studies on plant stress tolerance and immunology. We identified and analyzed gene families encoding these proteins in maize using computational and molecular biology approaches. Thirty genes were found to encode putative FKBPs according to their FK506-binding domain. The FKBP genes can be classified YH25448 into single domain and multiple domain members based on the number of the domains. By analysis of the physical locations, the 30 FKBP genes were found to be widely distributed on 10 chromosomes. After analysis of the FKBP phylogenetic tree in the maize genome, we found that the 30 genes revealed two major clades. Gene duplication played a major role in the evolution of FKBP genes, which suggests that the FKBP genes in maize have a pattern significantly different from that of these genes in rice. Based on semi-quantitative RT-PCR,

we found that the 30 FKBPs were expressed differently in Repotrectinib various tissues in maize, which suggests that FKBP genes play different roles in each tissue. Several FKBPs were expressed at higher levels in roots, indicating that these genes in maize may have similar or overlapping functions.”
“Protein-protein interactions are often mediated by flexible loops that experience conformational dynamics on the microsecond to millisecond time scales. NMR relaxation studies can map these dynamics. However, defining the network of inter-converting conformers that underlie the relaxation data remains generally challenging. Here, we combine NMR relaxation experiments with simulation to visualize networks of inter-converting

conformers. We demonstrate our approach with the apo Pin1-WW domain, for which NMR has revealed conformational dynamics of a flexible loop in the millisecond range. We sample and cluster the free energy landscape using Markov State Models (MSM) with major and minor exchange states with high correlation with the NMR relaxation https://www.selleckchem.com/CDK.html data and low NOE violations. These MSM are hierarchical ensembles of slowly interconverting, metastable macrostates and rapidly interconverting microstates. We found a low population state that consists primarily of holo-like conformations and is a “”hub” visited by most pathways between macrostates. These results suggest that conformational equilibria between holo-like and alternative conformers pre-exist in the intrinsic dynamics of apo Pin1-WW. Analysis using MutInf, a mutual information method for quantifying correlated motions, reveals that WW dynamics not only play a role in substrate recognition, but also may help couple the substrate binding site on the WW domain to the one on the catalytic domain.