Search

Proximal tubule endocytosis is essential to produce protein-free urine as well as to regulate system-wide metabolic pathways, such as the activation of Vitamin D. We have determined that the proximal tubule expresses an endolysosomal membrane protein, protein spinster homolog1 (Spns1), which engenders a novel iron conductance that is indispensable during embryonic development. Conditional knockout of Spns1 with a novel Cre-LoxP construct specific to megalin-expressing cells led to the arrest of megalin receptor-mediated endocytosis as well as dextran pinocytosis in proximal tubules. The endocytic defect was accompanied by changes in megalin phosphorylation as well as enlargement of lysosomes, confirming previous findings in Drosophila and Zebrafish. The endocytic defect was also accompanied by iron overload in proximal tubules. Remarkably, iron levels regulated the Spns1 phenotypes because feeding an iron-deficient diet or mating Spns1 knockout with divalent metal transporter1 knockout rescued the phenotypes. Conversely, iron-loading wild-type mice reproduced the endocytic defect. These data demonstrate a reversible, negative feedback for apical endocytosis and raise the possibility that regulation of endocytosis, pinocytosis, megalin activation, and organellar size and function is nutrient-responsive. NEW & NOTEWORTHY: Spns1 mediates a novel iron conductance essential during embryogenesis. Spns1 knockout leads to endocytic and lysosomal defects, accompanied by iron overload in the kidney. Reversal of iron overload by restricting dietary iron or by concurrent knockout of the iron transporter, DMT1 rescued the endocytic and organellar defects and reverted markers of iron overload. These data suggest feedback between iron and proximal tubule endocytosis. [ABSTRACT FROM AUTHOR]

Fungi of the genus Cryphonectria are of special interest to tree pathologists because they cause bark disease in numerous species of the Fagaceae and Betulaceae. Despite this special attention, several Cryphonectria species were not recognized as such for a long time. This also affected the identity of eight isolates with outdated names that have been deposited in our laboratory since 1954. The present study reconstructs the history of the Cryphonectria cultures M282–M289 using primary bibliographic sources. To verify the species identity, all isolates were DNA barcoded and taxonomic affiliation was assessed using a phylogenetic approach. The taxonomic identity combined with the history of the isolates confirms that the chestnut blight epidemic (Cryphonectria parasitica) in Spain was caused by the planting of Asian chestnuts and that the first documented case of bark canker in 1940 was caused by Cryphonectria radicalis on Japanese chestnuts imported from France. The history of isolate M289 could be traced back to CBS 165.32, which proved to be the oldest preserved isolate of the rare Cryphonectria naterciae, confirming the presence of this fungus in Europe for at least 100 years. Based on the ITS barcoding of the 32‐year‐old type specimen, Cryphonectria decipiens must be reclassified as a later synonym of Cryphonectria radicalis. The reconstruction of the history of isolates M282–M289 takes us on a scientific journey from Italy to France, Spain and Portugal in the early twentieth century and offers new insights into the historical context of the invasion of Cryphonectria parasitica in Europe. [ABSTRACT FROM AUTHOR]

The objective was to determine the effects of injectable vitamin E (VE) before or after transit on feedlot cattle receiving performance, health, and blood parameters. Angus × Simmental steers (n = 196; body weight [ BW ] = 163 ± 29 kg) were utilized in a randomized complete block design. Steers were blocked by BW and randomly assigned to 1 of 3 treatments: intramuscular injections of saline pre- and post-transit (CON), intramuscular injections of VE (2,000 mg d-α-tocopherol) pre-transit and saline post-transit (PRE), or intramuscular injections of saline pre-transit and VE (2,000 mg d-α-tocopherol) post-transit (POST). Pre-transit injections were administered on day 0, and steers were transported on day 7 for approximately 4 h (348 km). After arrival, steers were fed a common corn silage-based diet in GrowSafe bunks. Final BW tended to be greater (P = 0.08) for CON steers compared with POST steers while PRE steers were intermediate. From days 7 to 63, treatment affected average daily gain (ADG) with PRE and CON steers exhibiting (P = 0.04) greater ADG compared with POST steers. Dry matter intake (DMI), water intake, and gain to feed from days 7 to 63 were not affected (P ≥ 0.17) by treatment. Day 0 serum α-tocopherol concentrations were considered marginal (2.3 ± 0.2 mg/l). A treatment × day interaction (P < 0.01) was observed for serum α-tocopherol concentrations. Serum α-tocopherol concentrations were greatest for PRE steers on day 7 (prior to and post-transit), but greater for POST steers on dys 10 and 14. Plasma ferric-reducing antioxidant potential concentrations increased (P = 0.04) for POST steers compared with CON steers and PRE steers being intermediate. Plasma non-esterified fatty acids (NEFA) concentrations exhibited a treatment × day interaction (P = 0.04) with CON and POST steers being 16% and 14% greater than PRE steers on day 14, respectively. On day 21, NEFA concentrations were greatest for POST steers compared with PRE steers and CON steers being intermediate. There was no main effect (P ≥ 0.14) of treatment on the number of bovine respiratory disease morbidity treatments. Hair cortisol concentrations were decreased (P < 0.01) 14 days after transit for PRE and POST steers compared with CON steers. Overall, injectable VE administered before or after transit increased serum tocopherol concentrations while reducing stress, but did not improve the growth performance of beef steers during the receiving phase. [ABSTRACT FROM AUTHOR]

This study investigated the effects of injectable vitamin C (VC) at weaning and prior to transit on growth performance and immune function in early-weaned beef steers. On day 0, 91 Angus × Simmental steers (92 ± 4 kg) were weaned (65 ± 11 d of age), given vaccination boosters, blocked by age, and randomly assigned to weaning (WEAN) treatments: intramuscular injections (20 mL per steer) of VC (250-mg sodium ascorbate per mL; 5 g per steer) or saline (SAL). From days 0 to 48, steers were housed at the Dixon Springs Agricultural Center (Simpson, IL) in pens (six pens; N = 14 to 16 steers per pen) equipped with two to three Vytelle bunks to measure individual daily feed disappearance. On day 49, half of the steers in each WEAN treatment were randomly assigned to an additional injection treatment (20 mL per steer) of VC or SAL prior to transport (TRANS). After administering pretransit injections, all steers were loaded onto a commercial livestock trailer with equal representation of treatments across compartments. Steers were transported for 6 h (approximately 480 km) to the Illinois Beef and Sheep Field Laboratory (Urbana, IL). Upon arrival, steers were sorted into pens (six pens; N = 13 to 17 steers per pen) with 2 Vytelle bunks per pen. Steers were weighed on days 0, 1, 14, 48, 49, 64, 78, 106, and 107. Blood was collected (WEAN = 24 steers per treatment; TRANS = 12 steers per treatment) on days 0, 1, 2, 14, 49 (pre- and posttransit), 50, and 51. Data were analyzed using the MIXED procedure of SAS 9.4 with fixed effects of age block, WEAN, TRANS, and WEAN × TRANS. Plasma ascorbate concentrations were greater (WEAN × time P < 0.01) on days 1 and 2 for steers that received VC at weaning. Similarly, for steers that received VC on day 49 pretransit, ascorbate concentrations were greater (TRANS × time P = 0.04) on days 49 posttransit, 50, and 51. Treatments did not affect (P ≥ 0.13) body weight, average daily gain, or gain to feed throughout the trial. Serum Bovine Viral Diarrhea Virus type 1 and 2 antibody titers on days 14 and 51 were not affected (P ≥ 0.32) by treatment. Injectable VC administered to early-weaned beef steers at the time of weaning or pretransit increased plasma ascorbate concentrations but did not improve growth performance or antibody response to vaccination booster. [ABSTRACT FROM AUTHOR]

This study examined the effects of injectable vitamin C (VC) before transport and duration of transit on feedlot performance, inflammation, and muscle fatigue in cattle. One hundred thirty-two Angus-cross steers (393 ± 4 kg) were stratified by body weight (BW) to a 2 × 2 factorial of intramuscular injection (INJ; 20 mL/steer): VC (250 mg sodium ascorbate/mL) or saline (SAL) and road transit duration (DUR): 18 h (18-h; 1,770 km) or 8 h (8-h; 727 km). On day 0, steers were weighed and given INJ of VC or SAL immediately before transport. Upon return (day 1), BW and blood were collected before steers returned to pens equipped with GrowSafe bunks. Steers were weighed on days 0, 1, 7, 15, 30, 31, 54, and 55. Data were analyzed via ProcMixed of SAS (experimental unit = steer; 32 to 34 steers/treatment) with fixed effects of INJ, DUR, and the interaction. Blood was collected on days −5, 1, 2, 3, and 7 (n = 9 steers/treatment); blood parameters were analyzed as repeated measures with the repeated effect of day. Area under the curve (AUC) for plasma ferric reducing antioxidant power (FRAP) was calculated using R. Final BW was greater for 8 h compared to 18 h (P = 0.05) with no effect of INJ or interaction (P ≥ 0.51). Dry matter intake (DMI) from days 1 to 7 was greater for VC-8, intermediate for VC-18 and SAL-18, and least for SAL-8 (P = 0.02). Overall, DMI tended to be greatest for SAL-18, intermediate for VC-18 and VC-8, and least for SAL-8 (P = 0.08). Days 7 to 31 gain:feed (G:F) was greatest for VC-18 compared to other treatments (INJ × DUR, P = 0.05), and there was no effect of treatment on overall G:F (P ≥ 0. 19). There was no INJ or INJ × DAY (P ≥ 0.17) effect on serum lactate, haptoglobin, or non-esterified fatty acid. However, these blood parameters were greater on day 1 for 18 h compared to 8 h, and both treatments returned to near baseline by day 3 (DUR × DAY, P < 0.01). Plasma ascorbate concentrations on day 1 were greater for VC compared to SAL and returned to baseline by day 2 (INJ × DAY, P < 0.01). Plasma FRAP AUC from days −5 to 3 was greatest for VC-18, intermediate for VC-8 and SAL-8, and least for SAL-18 (INJ × DAY, P = 0.02). This suggests an antioxidant prior to long-haul transit positively influenced antioxidant capacity; however, VC did not improve overall post-transit performance. Although longer transit duration increased indicators of muscle fatigue and inflammation, post-transit performance was not appreciably different between transit durations. [ABSTRACT FROM AUTHOR]

Using the USA300, methicillin-resistant Staphylococcus aureus strain LAC, we previously examined the impact of regulatory mutations implicated in biofilm formation on protease production and virulence in a murine sepsis model. Here we examined the impact of these mutations in the USA200, methicillin-sensitive strain UAMS-1. Mutation of agr, mgrA, rot, sarA and sigB attenuated the virulence of UAMS-1. A common characteristic of codY, rot, sigB, and sarA mutants was increased protease production, with mutation of rot having the least impact followed by mutation of codY, sigB and sarA, respectively. Protein A was undetectable in conditioned medium from all four mutants, while extracellular nuclease was only present in the proteolytically cleaved NucA form. The abundance of high molecular weight proteins was reduced in all four mutants. Biofilm formation was reduced in codY, sarA and sigB mutants, but not in the rot mutant. Eliminating protease production partially reversed these phenotypes and enhanced biofilm formation. This was also true in LAC codY, rot, sarA and sigB mutants. Eliminating protease production enhanced the virulence of LAC and UAMS-1 sarA, sigB and rot mutants in a murine sepsis model but did not significantly impact the virulence of the codY mutant in either strain. Nevertheless, these results demonstrate that repressing protease production plays an important role in defining critical phenotypes in diverse clinical isolates of S. aureus and that Rot, SigB and SarA play critical roles in this regard. [ABSTRACT FROM AUTHOR]

We previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects. [ABSTRACT FROM AUTHOR]

Using the USA300, methicillin-resistant Staphylococcus aureus strain LAC, we previously examined the impact of regulatory mutations implicated in biofilm formation on protease production and virulence in a murine sepsis model. Here we examined the impact of these mutations in the USA200, methicillin-sensitive strain UAMS-1. Mutation of agr, mgrA, rot, sarA and sigB attenuated the virulence of UAMS-1. A common characteristic of codY, rot, sigB, and sarA mutants was increased protease production, with mutation of rot having the least impact followed by mutation of codY, sigB and sarA, respectively. Protein A was undetectable in conditioned medium from all four mutants, while extracellular nuclease was only present in the proteolytically cleaved NucA form. The abundance of high molecular weight proteins was reduced in all four mutants. Biofilm formation was reduced in codY, sarA and sigB mutants, but not in the rot mutant. Eliminating protease production partially reversed these phenotypes and enhanced biofilm formation. This was also true in LAC codY, rot, sarA and sigB mutants. Eliminating protease production enhanced the virulence of LAC and UAMS-1 sarA, sigB and rot mutants in a murine sepsis model but did not significantly impact the virulence of the codY mutant in either strain. Nevertheless, these results demonstrate that repressing protease production plays an important role in defining critical phenotypes in diverse clinical isolates of S. aureus and that Rot, SigB and SarA play critical roles in this regard. [ABSTRACT FROM AUTHOR]

We developed a quantum-chemical approach for ab initio calculations of metastable-induced electron-emission spectra (MIES). In contrast to earlier work, our calculation method accounts for the anisotropy of the MIES spectra with respect to not only the direction of incidence of metastable helium but also to that of electron detection. Since we can freely choose both, incidence and detection direction in our simulation, our method is able to reconstruct MIES spectra which are dominated by Auger deexcitation for any experimental setups and orientation of the studied molecules. Here, we study the dependence of the MIES spectrum on the incidence and detection direction and other experimental parameters and compare the results for the case of adsorbed benzene with experimental data. [ABSTRACT FROM AUTHOR]

Conformational disorder of conjugated polymers is an important issue to be understood and quantified. In this paper we present a new method to assess the chain conformation of conjugated polymers based on measurements of intrachain energy transfer. The chain conformation is modeled on the basis of monomer-monomer interactions, such as torsion, bending, and stretching of the connecting bond. The latter two potentials are assumed to be harmonic, while the torsional potential was calculated by density functional theory using B3-LYP functional with the SVP basis set. The energy transfer dynamics of excitons on these chains are quantitatively simulated using Förster-type line-dipole energy transfer. This allows us to compare the simulated ground state conformation of single polymer chains to ultrafast depolarization experiments of poly [3-(2,5-dioctylphenyl)thiophene] in solution. We identify torsional rotation as the main contributor to conformational disorder and find that this disorder is mainly controlled by the energy difference between syn and anti bonds. [ABSTRACT FROM AUTHOR]

We have studied biphenyl by time-dependent density-functional theory. In particular, we have analyzed the dependence of singlet excitation energies and transition dipoles on the torsional angle between the phenyl groups. The torsional spectrum has been computed quantum mechanically as well as semiclassically in order to understand how this influences the broadening of absorption and luminescence spectra. Our results are in best agreement with supersonic jet spectroscopy data, but also fit astonishingly well to spectra of biphenyl in condensed phase. Furthermore, we compare the torsional and vibrational relaxation and discuss qualitatively the general consequences for poly-para-phenylenes and related conjugated polymers as poly-thiophenes, considering, in particular, how side chains and solvents may affect the optical spectra. [ABSTRACT FROM AUTHOR]

We calculate the electronic states of the low bandgap polyfluorene-based copolymer DiO-PFDTBT, which consists of alternating 9,9-dioctyl-9H-fluorene and 4,7-di-thiophen-2-ylbenzo[1,2,5]thiadiazole (TBT) units, and compare with the steady-state absorption, emission, and excitation spectrum. Using the semiempirical quantum-chemical (ZINDO) method we can assign the characteristic bands of the “camel-back” absorption spectrum to one charge transfer state at lower energy localized on the TBT unit, and one delocalized excitonic state at higher energy corresponding to the π-conjugated electron system. Additional “dark” charge transfer states in the gap between these bands have been revealed. Calculations are also made on the red light emitting polyfluorene-based copolymer poly(fluorene-co-benzothiadiazole) (F8BT), which contains benzo[1,2,5]thiadiazole instead of TBT. The nature of the electronic states in F8BT and DiO-PFDTBT are found to be qualitatively the same. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

In conjugated polymers the optical excitation energy transfer is usually described as Förster-type hopping between so-called spectroscopic units. In the simplest approach using the point-dipole approximation the transfer rate is calculated based on the interaction between the transition dipoles of two spectroscopic units. In the present work we compare this approach with three others: The line-dipole approximation, the Coulomb integral between the transition densities, and a quantum-chemical calculation of the interacting dimer as entity. The latter two approaches are based on the semiempirical method ZINDO. The line-dipole approximation is an attractive compromise between computational effort and precision for calculations of the excitonic coupling in extended conjugated polymers. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

In the present work we will demonstrate that the nuclear dynamics have a strong influence on the delocalization of an exciton in a dimer, even if they do not effect the excitonic interaction. It will be shown that the internal nuclear conformation of the molecules forming the dimer depends critically on the delocalization of the exciton state in the dimer and vice versa. The resulting closed loop enforces a localization of the lower excitonic state, but, contrary to the commonly accepted view, a delocalization of the upper one. Qualitatively different time-evolution of the delocalization length for the lower and upper excitonic state will be shown. Besides, it will turn out that the nuclear motions inhibit a complete delocalization of the excitonic state in any case. To accomplish nuclear and exciton dynamics, the nonadiabatic coupling between the two excitonic states will be deduced. This causes a relaxation from the upper to the lower excitonic state, which limits the maximum reachable exciton delocalization. [ABSTRACT FROM AUTHOR]

Background: Phosphatidylcholine coatings have been shown to elute antibiotics for several days. A recently developed biofilm inhibitor, cis-2-decenoic acid (C2DA), has been shown to exhibit synergistic activity with several common antibiotics. This study aims to evaluate the effectiveness of C2DA and amikacin dual drug delivery from a phosphatidylcholine coating.Questions/purposes: (1) What are the in vitro elution profiles of amikacin and C2DA from phosphatidylcholine-coated coupons in incubated phosphate-buffered saline? (2) Does the presence of C2DA in eluate samples lower the amount of amikacin needed for bacterial inhibition in overnight bacterial turbidity assays? (3) Does addition of amikacin and C2DA result in decreased colony-forming units (CFUs) on wire implants and bone when compared with phosphatidylcholine coatings alone in a mouse model of periprosthetic joint infection?Methods: Effects of loading concentrations were assessed during 7-day in vitro elution studies for coatings containing all mixtures of 0%, 5%, 15%, and 25% wt of amikacin and C2DA (n = 4) through quantitative high-performance liquid chromatography concentration determination and plotting concentration eluted over time. Antimicrobial activity was assessed by overnight turbidity testing of elution study samples against Staphylococcus aureus or Pseudomonas aeruginosa. In vivo efficacy was assessed using phosphatidylcholine-coated wire implants in a murine (mouse) model of infection (n = 3). Wire implants were coated with phosphatidylcholine containing no antimicrobials, amikacin alone, C2DA alone, or amikacin and C2DA and then inserted into the intramedullary femur of each mouse and inoculated with S aureus. The number of viable bacterial colonies on the implant surface and in the surrounding bone was determined after 1 week with the goal of achieving complete bacterial clearance. Total viable CFU count and proportion of samples achieving complete clearance were compared between groups.Results: Elution samples showed a burst response of amikacin and C2DA for 1 to 2 days with C2DA release continuing at low levels through Day 4. All tested eluate samples inhibited P aeruginosa. Samples from coatings containing 25% amikacin or 15% amikacin and any amount of C2DA were able to inhibit S aureus formation, but all coatings with 5% amikacin or 15% amikacin but no C2DA were not inhibitory. All in vivo treatment groups achieved complete bacterial clearance on the wire implant, and the C2DA alone and amikacin alone coatings cleared all CFUs in bone (pin: phosphatidylcholine only one of three; amikacin three of three, C2DA three of three, amikacin + C2DA three of three, p = 0.04 [Fisher's exact test]; bone: coating only: zero of three; amikacin: three of three; C2DA; three of three; C2DA + amikacin: one of three; p = 0.03 [Fisher's exact test]).Conclusions: Phosphatidylcholine coatings elute antimicrobials in vitro under infinite sink conditions for up to 4 days in phosphate-buffered saline and were able to reduce bacterial colonies in a preliminary in vivo model. Turbidity testing with eluate samples containing varying amounts of C2DA and amikacin agrees with previous studies showing synergy between them.Clinical Relevance: Used as an adjunctive to systemic therapy, C2DA-loaded phosphatidylcholine coatings have potential value as a prophylactic infection prevention measure. Future studies may include different antibiotics, animal studies with larger sample sizes and more controls, and advanced coating delivery methods. [ABSTRACT FROM AUTHOR]

Examines the use of nonlinear polarization spectroscopy in the frequency domain (NLPF) to analyze the substructure of molecular optical absorption band. Deduction of NLPF spectra for systems with optical transition; Details on ultrafast processes in complex molecular and supermolecular systems; Description of NLPF spectra of supermolecular systems.

Albuminuria acts as a marker of progressive chronic kidney disease and as an indicator for initiation of hypertension treatment via modulation of the renin-angiotensin-aldosterone system with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors. However, the true significance of albuminuria has yet to be fully defined. Is it merely a marker of underlying pathophysiology, or does it play a causal role in the progression of kidney disease? The answer remains under debate. In this issue of the JCI, Bedin et al. used next-generation sequencing data to identify patients with chronic proteinuria who had biallelic variants in the cubilin gene (CUBN). Through investigation of these pathogenic mutations in CUBN, the authors have further illuminated the clinical implications of albuminuria. [ABSTRACT FROM AUTHOR]

Albuminuria acts as a marker of progressive chronic kidney disease and as an indicator for initiation of hypertension treatment via modulation of the renin-angiotensin-aldosterone system with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors. However, the true significance of albuminuria has yet to be fully defined. Is it merely a marker of underlying pathophysiology, or does it play a causal role in the progression of kidney disease? The answer remains under debate. In this issue of the JCI, Bedin et al. used next-generation sequencing data to identify patients with chronic proteinuria who had biallelic variants in the cubilin gene (CUBN). Through investigation of these pathogenic mutations in CUBN, the authors have further illuminated the clinical implications of albuminuria. [ABSTRACT FROM AUTHOR]

Complex extremity wounds in Wounded Warriors can become contaminated with microbes, which may cause clinical outcomes resulting in amputation, morbidity, or even fatality. Local delivery of multiple or broad-spectrum antibiotics allows practicing clinicians treatment solutions that may inhibit biofilm formation. Propagation of vancomycin-resistant Staphylococcus aureus is also a growing concern. The development of vancomycin-resistant S. aureus has become a critical challenge in nosocomial infection prevention in the USA, but to date has seen little occurrence in osteomyelitis. As an alternative, locally delivered ciprofloxacin and rifampin were investigated in a preclinical model for the prevention of biofilm in complex extremity wounds with implanted fixation device. In vitro assays demonstrated ciprofloxacin and rifampin possess an additive effect against Gram-negative Pseudomonas aeruginosa and were actively eluted from a chitosan sponge based local delivery system. In an in vivo orthopedic hardware-associated polymicrobial model (S. aureus and Escherichia coli) the combination was able to achieve complete clearance of both bacterial strains. E. coli was detected in bone of untreated animals, but did not form biofilm on wires. Results reveal the clinical potential of antibiotic-loaded chitosan sponges to inhibit infection through tailored antibiotic selection at desired concentrations with efficacy towards biofilm inhibition. [ABSTRACT FROM AUTHOR]

Pseudodidymella fagi is a leaf blotch pathogen of Fagus crenata in Japan. This pathogen is now reported for the first time on F. sylvatica in Switzerland and Germany. Species identity was verified by morphological assessment of the asexual and sexual morphs and by comparing the internal transcribed spacer ( ITS) sequence of the type material from Japan and of freshly collected samples from Europe. ITS sequences proofed to be completely identical. The asexual morph Pycnopleiospora of Ps. fagi is formed on necrotic leaf spots during summer and autumn. In early spring, its sexual morph is formed in the litter of F. sylvatica. The connection between sexual and asexual morphs was verified by sequencing the ITS region of single conidium and ascospore isolates. The pathogenicity of Ps. fagi on F. sylvatica was tested by inoculations on detached leaves in vitro and Koch's postulates were fulfilled. The second pathogen we report in central Europe for the first time is Petrakia deviata, which causes a leaf blotch disease of field maple ( Acer campestre). This species was collected only once in the central Caucasus region in 1929 and was never found again after its first discovery. Now it was rediscovered in two different locations in Switzerland on field maple ( A. campestre) and on the new host Norway maple ( A. platanoides). Species identity was verified by morphology and by comparison with the ITS sequence of the holotype specimen and freshly collected samples. Phylogenetic analysis based on ITS sequences suggested that Ps. fagi and P. deviata are closely related to each other. Whether these species were simply overlooked so far, profit from climate change, or represent newly introduced invasive species remains to be studied. Moreover, deeper phylogenetic analysis using multiple sequence markers should be conducted to verify species identities. [ABSTRACT FROM AUTHOR]

We investigated the intercalation of C60 into poly(p-anthracene-ethynylene)-alt-poly(p-phenylene-vinylene) copolymers layers by density functional theory calculations in respect of crystal structures and electronic band structures. Based on the experimental observations, we found that the copolymer with branched side chains substituted next to the anthracene units and the linear side chains substituted to the vinylene units has a better tendency to intercalate with C60 than the reversely substituted copolymer. The calculated electronic band structures of the intercalated phase, featured by flat in-gap states resulting from C60 molecules, explain the experimentally observed variations of the photocurrent, photoluminescence, and electroluminescence yields with different ratio between PCBM and the two types of copolymers in the ternary blend. [ABSTRACT FROM AUTHOR]

The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in endocytosis and are implicated in diseases of the kidney and brain. Here, we report high-resolution cryoelectron microscopy structures of LRP2 isolated from mouse kidney, at extracellular and endosomal pH. The structures reveal LRP2 to be a molecular machine that adopts a conformation for ligand binding at the cell surface and for ligand shedding in the endosome. LRP2 forms a homodimer, the conformational transformation of which is governed by pH-sensitive sites at both homodimer and intra-protomer interfaces. A subset of LRP2 deleterious missense variants in humans appears to impair homodimer assembly. These observations lay the foundation for further understanding the function and mechanism of LDL receptors and implicate homodimerization as a conserved feature of the LRP receptor subfamily. [Display omitted] • Cryo-EM structures of full-length LRP2 purified from mouse kidney are determined • LRP2 adopts a homodimer assembly at both pH 7.5 and pH 5.2 • pH-sensitive transformations of the homodimer regulate ligand binding and release • Missense variants at pH-sensitive sites associate with loss of function in humans Structures of full-length native mouse LRP2 reveal that it is a homodimer that undergoes dramatic pH-dependent structural transitions that renders it ligand-receptive at the cell surface and ligand-shedding in endosomes. [ABSTRACT FROM AUTHOR]

In this work, we report an in-depth investigation on the π-stacking and interdigitating structures of poly(p-anthracene-ethynylene)-alt-poly(p-phenylene-vinylene) copolymer with octyl and ethyl-hexyl side chains and the resulting electronic band structures using density functional theory calculations. We found that in the π-stacking direction, the preferred stacking structure, determined by the steric effect of the branched ethyl-hexyl side chains, is featured by the anthracene-ethynylene units stacking on the phenylene-vinylene units of the neighboring chains and vice versa. This stacking structure, combined with the interdigitating structure where the branched side chains of the laterally neighboring chains are isolated, defines the energetically favorable structure of the ordered copolymer phase, which provides a good compromise between light absorption and charge-carrier transport. [ABSTRACT FROM AUTHOR]

Free-basecorroles exist as individual NH-tautomers that may differin their spectral and chemical properties. The present paper focuseson the origin of the basicity difference between two AB2-pyrimidinylcorrole NH-tautomers, which has been tentatively attributedto differences in the weak out-of-plane distortions of the pyrrolenicring between two NH-tautomers. Using DFT-geometry optimizations, weshow that the pyrroles involved in the NH-tautomerization processare approximately in-plane, whereas the other two pyrroles are tiltedout-of-plane in opposite directions. Alternative out-of-plane distortionpatterns play a minor role, as revealed by ab initiomolecular dynamics simulations. Given that the protonated corroleis a unique species, the energy difference between the two NH-tautomersequals the difference in protonation driving force between them. Thisenergy difference increases with improved theoretical level of accountingfor intermolecular interactions and dielectric screening of surfacecharges. The different charge distributions of the two NH-tautomersresult in electrostatic potential distributions that effect a largerproton attraction in the case of the T1 tautomer than in the caseof the T2 tautomer. In summary, our quantum chemical results showclearly a higher basicity of the T1 tautomer as compared to the T2tautomer: The previously assumed pronounced out-of-plane tilt of theT1-nonprotonated nitrogen is verified by ab initiomolecular dynamics simulations. Together with analysis of the electrostaticpotential distribution we show that the nonprotonated nitrogen isnot only tilted stronger but also significantly more accessible forprotons in the case of T1 as compared to T2. Additionally, the thermodynamicbasicity is higher for T1 than for T2. [ABSTRACT FROM AUTHOR]

The article presents case study of a 18-year-old right-hand dominant woman, who had enlarged right medial elbow mass and disturbed paresthesias. It states that though the patient had no past history of soft tissue tumors, neurocutaneous disorders and neuropathy, yet the soft tissue mass of the patient's right elbow was found to be elongated. It discusses that the blood cell count was found normal, and further examination of the patient led to diagnosis of Intraneural perineurioma.

ABSTRACT Polymicrobial musculoskeletal wound infections are troublesome complications and can be difficult to treat when caused by invasive fungi or bacteria. However, few local antifungal delivery systems have been studied. Chitosan and polyethylene glycol (PEG) sponge local antifungal delivery systems have been developed for adjunctive therapy to reduce musculoskeletal wound contamination. This study evaluated the effects of blending PEG, at 6,000 or 8,000 g/mol, with chitosan in sponge form on in vitro amphotericin B and vancomycin elution, eluate activity, cytocompatibility, and in vivo prevention of a bacterial biofilm. Blended chitosan sponges released both amphotericin B and vancomycin in vitro. All tested amphotericin B eluates remained active against Candida albicans, and vancomycin eluates from blended sponges maintained activity against Staphylococcus aureus. Amphotericin B eluates obtained after 1 h from blended sponges elicited 62-95% losses in fibroblast viability, but 3 h eluates only caused 22-60% decreases in viability. In a Staphylococcus aureus infected mouse catheter biofilm prevention model, vancomycin loaded chitosan/PEG 6000 sponge cleared bacteria from 100% of the catheters, with reduced clearance rate observed in other sponges. These results indicate that the chitosan/PEG blended sponges have potential for local antifungal and/or antibiotic combination delivery as an adjunctive therapy to prevent wound infections. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???-???, 2015. [ABSTRACT FROM AUTHOR]

We demonstrate that coating calcium sulfate with deacetylated chitosan enhances the elution profile of daptomycin by prolonging the period during which high concentrations of antibiotic are released. Coatings reduced initial bolus release of daptomycin by a factor of 10 to approximately 1000 µg/ml, and levels remained above 100 µg/ml for up to 10 days. Chitosan-coated and uncoated calcium sulfate implants with and without 15% daptomycin were evaluated in an experimental model of staphylococcal osteomyelitis through bacteriology scores, radiology, histopathology, and Gram staining. Significant reduction in bacteriology scores was observed for implants containing daptomycin and coated with chitosan compared with all the other groups. We confirm that the use of chitosan-coated calcium sulfate beads for local antibiotic delivery can be correlated with an improved therapeutic outcome following surgical debridement in the treatment of chronic osteomyelitis. [ABSTRACT FROM AUTHOR]

We investigated the in vivo relevance of the impact of sarA and saeRS on protease production using derivatives of the USA300 strain LAC. The results confirmed that mutation of saeRS or sarA reduces virulence in a bacteremia model to a comparable degree. However, while eliminating protease production restored virulence in the sarA mutant, it had little impact in the saeRS mutant. Additionally, constitutive activation of saeRS ( saeRSC) enhanced the virulence of LAC and largely restored virulence in the isogenic sarA mutant. Based on these results, together with our analysis of the representative virulence factors alpha toxin, protein A ( Spa), and extracellular nucleases, we propose a model in which the attenuation of saeRS mutants is defined primarily by decreased production of such factors, while constitutive activation of saeRS increases virulence, and reverses the attenuation of sarA mutants, because it results in both increased production and decreased protease-mediated degradation of these same factors. This regulatory balance was also apparent in a murine model of catheter-associated infection, with the results suggesting that the impact of saeRS on nuclease production plays an important role during the early stages of these infections that is partially offset by increased protease production in sarA mutants. [ABSTRACT FROM AUTHOR]

The individual absorption spectraof the two NH tautomers of 10-(4,6-dichloropyrimidin-5-yl)-5,15-dimesitylcorroleare assigned on the basis of the Gouterman four-orbital model anda quantum chemical TD-DFT study. The assignment indicates that thered-shifted T1 tautomer is the one with protonated pyrrole nitrogenatoms N(21), N(22) and N(23), whereas the blue-shifted T2 tautomerhas pyrrole nitrogen atoms N(21), N(22) and N(24) protonated. A wave-likenonplanar distortion of the macrocycle in the ground state is foundfor both NH tautomers, with the wave axis going through the pyrrolescontaining N(22) and N(24). The 7C plane determined by the least-squaresdistances to the carbon atoms C1, C4, C5, C6, C9, C16, and C19 issuggested as a mean corrole macrocycle plane for the analysis of out-of-planedistortions. The magnitude of these distortions is distinctly differentfor the two NH tautomers, leading to substantial perturbations oftheir acid–base properties, which are rationalized by the interplayof the degree of out-of-plane distortion of the macrocycle as a wholeand the tendency of the pyrrole nitrogen atoms toward pyramidalization,with the former leading to a basicity increase whereas the latterenhances the acidity. [ABSTRACT FROM AUTHOR]

Protein polymer-based hydrogels have shown potential for tissue engineering applications, but require biocompatibility testing for in vivo use. Enzymatically crosslinked protein polymer-based hydrogels were tested in vitro and in vivo to evaluate their biocompatibility. Endotoxins present in the hydrogel were removed by Trition X-114 phase separation. The reduction of endotoxins decreased TNF-α production by a macrophage cell line in vitro; however, significant inflammatory response was still present compared to collagen control gels. A branched PEG molecule and dexamethasone were added to the hydrogel to reduce the response. In vitro testing showed a decrease in the TNF-α levels with the addition of dexamethasone. In vivo implantations into the epididymal fat pad of C57/BL6 mice, however, indicated a decreased inflammatory mediated immune response with a hydrogel treated with both PEGylation and endotoxin reduction. This study demonstrates the importance of endotoxin testing and removal in determining the biocompatibility of biomaterials. [ABSTRACT FROM PUBLISHER]

Mutation of staphylococcal accessory regulator ( sarA) results in increased production of extracellular proteases in Staphylococcus aureus, which has been correlated with decreased biofilm formation and decreased accumulation of extracellular toxins. We used murine models of implant-associated biofilm infection and S. aureus bacteraemia ( SAB) to compare virulence of USA300 strain LAC, its isogenic sarA mutant, and derivatives of each of these strains with mutations in all 10 of the genes encoding recognized extracellular proteases. The sarA mutant was attenuated in both models, and this was reversed by eliminating production of extracellular proteases. To examine the mechanistic basis, we identified proteins impacted by sarA in a protease-dependent manner. We identified 253 proteins where accumulation was reduced in the sarA mutant compared with the parent strain, and was restored in the sarA/protease mutant. Additionally, in SAB, the LAC protease mutant exhibited a hypervirulent phenotype by comparison with the isogenic parent strain, demonstrating that sarA also positively regulates production of virulence factors, some of which are subject to protease-mediated degradation. We propose a model in which attenuation of sarA mutants is defined by their inability to produce critical factors and simultaneously repress production of extracellular proteases that would otherwise limit accumulation of virulence factors. [ABSTRACT FROM AUTHOR]

Abstract: Pancreatic islet encapsulation within biosynthetic materials has had limited clinical success due to loss of islet function and cell death. As an alternative encapsulation material, a silk-based scaffold was developed to reestablish the islet microenvironment lost during cell isolation. Islets were encapsulated with ECM proteins (laminin and collagen IV) and mesenchymal stromal cells (MSCs), known to have immunomodulatory properties or to enhance islet cell graft survival and function. After a 7 day in vitro encapsulation, islets remained viable and maintained insulin secretion in response to glucose stimulation. Islets encapsulated with collagen IV, or laminin had increased insulin secretion at day 2 and day 7, respectively. A 3.2-fold synergistic improvement in islet insulin secretion was observed when islets were co-encapsulated with MSCs and ECM proteins. Furthermore, encapsulated islets had increased gene expression of functional genes; insulin I, insulin II, glucagon, somatostatin, and PDX-1, and lower expression of the de-differentiation genes cytokeratin 19 and vimentin compared to non-encapsulated cells. This work demonstrates that encapsulation in silk with both MSCs and ECM proteins enhances islet function and with further development may have potential as a suitable platform for islet delivery in vivo. [Copyright &y& Elsevier]

Dasyspora gregaria, the single species of the allegedly monotypic rust genus Dasyspora (Basidiomycota, Pucciniales), was investigated by light microscopy and DNA sequencing (ITS1-5.8S-ITS2 region, partial LSU and SSU of the nuclear rDNA, mt cytochrome oxidase subunit 3). Both methods indicated that D. gregaria is not a single species but can be split in 11 distinct taxa, each of which appear confined to a single Xylopia species (Annonaceae) host. Herein nine of these are described as new. Both the phylogenetic analyses and morphology show that the species are grouped into two main clades designated Dasyspora gregaria and D. winteri. The first comprises D. gregaria, the type species of the genus, which is restricted to X. cayennensis, two new species on X. aromatica, D. segregaria from northern South America and D. echinata from Brazil. The second clade is formed by D. winteri, recombined from Puccinia winteri on X. sericea, and the new species D. amazonica on X. amazonica, D. emarginatae on X. emarginata, D. frutescentis on X. frutescens, D. ferrugineae on X. frutescens var. ferruginea, D. guianensis on X. benthamii, D. mesoamericana on X. frutescens, and D. nitidae on X. nitida. Dasyspora frutescentis and D. mesoamericana were not clearly distinguishable by their morphology and host associations but differed from another in their sequences and geographic distributions. They are considered cryptic species. An identification key and the distributions are given for all recognized species. Along with molecular data we discuss the systematic position of Dasyspora in the Pucciniales [ABSTRACT FROM AUTHOR]

Tissue-specific alternative splicing in the second half of Iglike domain 3 (D3) of fibroblast growth factor receptors 1-3 (FGFR1 to -3) generates epithelial FGFR1b-FGFR3b and mesenchymal FGFR1c-FGFR3c splice isoforms. This splicing event establishes a selectivity filter to restrict the ligand binding specificity of FGFRb and FGFRc isoforms to mesenchymally and epithelially derived fibroblast growth factors (FGFs), respectively. FGF1 is termed the "universal FGFR ligand" because it overrides this specificity barrier. To elucidate the molecular basis for FGF1 cross-reactivity with the "b" and "c" splice isoforms of FGFRs, we determined the first crystal structure of FGF1 in complex with an FGFRb isoform, FGFR2b, at 2.1 Å resolution. Comparison of the FGF1-FGFR2b structure with the three previously published FGF1-FGFRc structures reveals that plasticity in the interactions of the N-terminal region of FGF1 with FGFR D3 is the main determinant of FGF1 cross-reactivity with both isoforms of FGFRs. In support of our structural data, we demonstrate that substitution of three N-terminal residues (Gly-19, His-25, and Phe-26) of FGF2 (a ligand that does not bind FGFR2b) for the corresponding residues of FGF1 (Phe-16, Asn- 22, and Tyr-23) enables the FGF2 triple mutant to bind and activate FGFR2b. These findings taken together with our previous structural data on receptor binding specificity of FGF2, FGF8, and FGF10 conclusively show that sequence divergence at the N termini of FGFs is the primary regulator of the receptor binding specificity and promiscuity of FGFs. [ABSTRACT FROM AUTHOR]

Seven species of the rust genus Sphaero-phragmium occur on members of the tropical plant family Annonaceae. Uropyxis gerstneri is recombined to S. gerstneri. A new species, S. xylopiae, is described from Xylopia acutiflora. The host plant of S. boanens is identified as Mitrella sp. Sphaerophragmium pulchrum is transferred to Dicheirinia. The anatomy of telia with teliospores and parasitizing mycelium is described and illustrated in detail. A new type of M-haustorium, which emanates laterally from intracellular hypha, is detected in S. monodorae. An identification key is given. [ABSTRACT FROM AUTHOR]

Background: The accessory gene regulator (agr) and staphylococcal accessory regulator (sarA) play opposing roles in Staphylococcus aureus biofilm formation. There is mounting evidence to suggest that these opposing roles are therapeutically relevant in that mutation of agr results in increased biofilm formation and decreased antibiotic susceptibility while mutation of sarA has the opposite effect. To the extent that induction of agr or inhibition of sarA could potentially be used to limit biofilm formation, this makes it important to understand the epistatic relationships between these two loci. Methodology/Principal Findings: We generated isogenic sarA and agr mutants in clinical isolates of S. aureus and assessed the relative impact on biofilmformation. Mutation of agr resulted in an increased capacity to forma biofilmin the 8325-4 laboratory strain RN6390 but had little impact in clinical isolates S. aureus. In contrast, mutation of sarA resulted in a reduced capacity to form a biofilm in all clinical isolates irrespective of the functional status of agr. This suggests that the regulatory role of sarA in biofilm formation is independent of the interaction between sarA and agr and that sarA is epistatic to agr in this context. This was confirmed by demonstrating that restoration of sarA function restored the ability to form a biofilm even in the corresponding agr mutants. Mutation of sarA in clinical isolates also resulted in increased production of extracellular proteases and extracellular nucleases, both of which contributed to the biofilm-deficient phenotype of sarA mutants. However, studies comparing different strains with and without proteases inhibitors and/or mutation of the nuclease genes demonstrated that the agr-independent, sarA-mediated repression of extracellular proteases plays a primary role in this regard. Conclusions and Significance: The results we report suggest that inhibitors of sarA-mediated regulation could be used to limit biofilm formation in S. aureus and that the efficacy of such inhibitors would not be limited by spontaneous mutation of agr in the human host. [ABSTRACT FROM AUTHOR]

The family of fibroblast growth factors (FGFs) regulates a plethora of developmental processes, including brain patterning, branching morphogenesis and limb development. Several mitogenic, cytoprotective and angiogenic therapeutic applications of FGFs are already being explored, and the recent discovery of the crucial roles of the endocrine-acting FGF19 subfamily in bile acid, glucose and phosphate homeostasis has sparked renewed interest in the pharmacological potential of this family. This Review discusses traditional applications of recombinant FGFs and small-molecule FGF receptor kinase inhibitors in the treatment of cancer and cardiovascular disease and their emerging potential in the treatment of metabolic syndrome and hypophosphataemic diseases. [ABSTRACT FROM AUTHOR]

Abstract: The excited states of fullerene–oligothiophene dyads were studied by quantum-chemical methods in respect of their theoretical suitability as solar-cell materials. Compared to the constituents a significant extension of the absorption spectra to the red has been found caused by optically excitable charge transfer states. These states seem to be responsible for the low energy conversion efficiency of fullerene–oligothiophene dyads in photovoltaic devices. [Copyright &y& Elsevier]

Abstract: The optimized geometries of bithiophene in the electronic ground and excited state have been calculated by time-dependent density functional theory using the hybrid functional B3-LYP. The dependence of the singlet excitation energies and transition dipoles on the torsion between the two thienyl groups has been determined and compared with the torsional potential curve previously found for biphenyl. Based on these data the torsional progressions in absorption and emission have been computed quantum-mechanically in order to show their contribution to the inhomogeneous broadening in the respective spectra of bithiophene. [Copyright &y& Elsevier]

The northern hemisphere tree genus Acer comprises 124 species, most of them monoecious, but 13 dioecious. The monoecious species flower dichogamously, duodichogamously (male, female, male), or in some species heterodichogamously (two morphs that each produce male and female flowers but at reciprocal times). Dioecious species cannot engage in these temporal strategies. Using a phylogeny for 66 species and subspecies obtained from 6600 nucleotides of chloroplast introns, spacers, and a protein-coding gene, we address the hypothesis (Pannell and Verdú, Evolution 60: 660–673. 2006) that dioecy evolved from heterodichogamy. This hypothesis was based on phylogenetic analyses ( Gleiser and Verdú , New Phytol. 165: 633–640. 2005) that included 29–39 species of Acer coded for five sexual strategies (duodichogamous monoecy, heterodichogamous androdioecy, heterodichogamous trioecy, dichogamous subdioecy, and dioecy) treated as ordered states or as a single continuous variable. When reviewing the basis for these scorings, we found errors that together with the small taxon sample, cast doubt on the earlier inferences. Based on published studies, we coded 56 species of Acer for four sexual strategies, dioecy, monoecy with dichogamous or duodichogamous flowering, monoecy with heterodichogamous flowering, or labile sex expression, in which individuals reverse their sex allocation depending on environment–phenotype interactions. Using Bayesian character mapping, we infer an average of 15 transformations, a third of them involving changes from monoecy-cum-duodichogamy to dioecy; less frequent were changes from this strategy to heterodichogamy; dioecy rarely reverts to other sexual systems. Contra the earlier inferences, we found no switches between heterodichogamy and dioecy. Unexpectedly, most of the species with labile sex expression are grouped together, suggesting that phenotypic plasticity in Acer may be a heritable sexual strategy. Because of the complex flowering phenologies, however, a concern remains that monoecy in Acer might not always be distinguishable from labile sex expression, which needs to be addressed by long-term monitoring of monoecious trees. The 13 dioecious species occur in phylogenetically disparate clades that date back to the Late Eocene and Oligocene, judging from a fossil-calibrated relaxed molecular clock. [ABSTRACT FROM AUTHOR]

Ectomycorrhizae (ECM) of Lactarius aff. omphaliformis Romagn., Russula alnijorullensis (Sing.) Sing. and Cortinarius tucumanensis Mos. on Andean alder (Alnus acuminata Kunth) were characterized and identified. The identification of the fungal symbionts was achieved by morpho-anatomical observations of mycorrhizae and by comparison of ITS-RFLP patterns obtained from ECM and fruitbodies. L. aff. omphaliformis ECM differed in some morphological details such as ramification and mantle type from ECM of the same species on A. glutinosa. L. aff. omphaliformis ECM show an orange to ochre mantle containing latex cells, which stain with sulpho-vanillin, emanating hyphae without clamps. R. alnijorullensis ECM represent a typical Russula-type-ECM, light yellow to pinkish, the outer mantle being composed of triangular latex-filled cells staining with sulpho-vanillin, emanating hyphae without clamps. C. tucumanensis ECM exhibit a white (silvery) to yellowish brown mantle covered with soil particles, emanating hyphae with clamps. [ABSTRACT FROM AUTHOR]

We previously demonstrated that mutation of the staphylococcal accessory regulator (sarA) in a clinical isolate of Staphylococcus aureus (UAMS-1) results in an impaired capacity to form a biofilm in vitro (K. E. Beenken, J. S. Blevins, and M. S. Smeltzer, Infect. Immun. 71:4206-4211, 2003). In this report, we used a murine model of catheter-based biofilm formation to demonstrate that a UAMS-1 sara mutant also has a reduced capacity to form a biofilm in vivo. Surprisingly, mutation of the UAMS-1 ica locus had little impact on biofilm formation in vitro or in vivo. In an effort to identify additional loci that might be relevant to biofilm formation and/or the adaptive response required for persistence of S. aureus within a biofilm, we isolated total cellular RNA from UAMS-1 harvested from a biofilm grown in a flow cell and compared the transcriptional profile of this RNA to RNA isolated from both exponential- and stationary-phase planktonic cultures. Comparisons were done using a custom-made Affymetrix GeneChip representing the genomic complement of six strains of S. aureus (COL, N315, Mu50, NCTC 8325, EMRSA-16 [strain 252], and MSSA-476). The results confirm that the sessile lifestyle associated with persistence within a biofilm is distinct by comparison to the lifestyles of both the exponential and postexponential phases of planktonic culture. Indeed, we identified 48 genes in which expression was induced at least twofold in biofilms over expression under both planktonic conditions. Similarly, we identified 84 genes in which expression was repressed by a factor of at least 2 compared to expression under both planktonic conditions. A primary theme that emerged from the analysis of these genes is that persistence within a biofilm requires an adaptive response that limits the deleterious effects of the reduced pH associated with anaerobic growth conditions. [ABSTRACT FROM AUTHOR]

In conjugated polymers the concept of spectroscopic units belonging to different spatial segments of the chain, which are responsible for the spectroscopic properties of the polymer, has been used to explain the spectral heterogeneity and the excitation migration by (Förster type) hopping transfer. In the present work we study the possible mechanism of segmentation of polythiophene into spectroscopic units by using quantum-chemical methods (ZINDO). We found that static geometric defects such as kinks or torsions do not result in a significant localization of the excited states to a certain segment. Hence, we propose that a dynamic localization of excitation due to the interaction between the nuclear and electronic degrees of freedom is responsible for the formation of the spectroscopic units. [ABSTRACT FROM AUTHOR]

Real-space collective excitation dynamics in molecular aggregates is studied using a model where the electronic system is described via exciton theory with surface hopping. The nuclear dynamics are included using the Langevin equation where temperature and zero-point motions are entered via the fluctuation-dissipation theorem. Dynamic processes like exciton relaxation, localization, polaron formation and diffusion of self-trapped excitons, which commonly require different theories, are simultaneously described with our approach. Numerical simulations of small linear aggregates are performed. Contrary to the common view we show that exciton relaxation can temporarily increase exciton delocalization. The results are discussed based on the photosynthetic light-harvesting pigment-protein complexes. [Copyright &y& Elsevier]

Background: Dysplastic oral leukoplakia (DOL) has been the index lesion in prevention trials for upper aerodigestive tract squamous cell carcinoma (SCC). Vitamin A derivatives, including 13-cis retinoic acid (13-CRA), have been used to treat DOL and to reduce the risk of subsequent SCC. Results from a trial of 13-CRA in patients with DOL are presented here. Transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor receptor messenger RNA (mRNA) expression were studied to validate their use as surrogate endpoint biomarkers in prevention trials for SCC.Study Design: In a prospective, randomized, double-blind trial of 13-CRA in 28 patients with DOL, TGF-alpha and epidermal growth factor receptor mRNA expression were analyzed in sequential biopsy specimens of DOL and of adjacent normal-appearing mucosa, utilizing a quantitative, competitive, reverse transcriptase polymerase chain reaction and were compared using the Wilcoxon signed-rank test for paired comparisons.Results: In biopsy specimens of DOL, TGF-alpha mRNA expression at baseline, but not baseline expression of epidermal growth factor receptor mRNA, was significantly elevated when compared with its expression in specimens from adjacent normal-appearing mucosa (p = 0.003). In patients randomized to 13-CRA who had > or = 50% clearance of DOL during treatment, significant modulation of TGF-alpha mRNA overexpression was seen after 6 months of treatment (p = 0.016). TGF-alpha mRNA overexpression at baseline predicted a subsequent response to 13-CRA (p 0.066).Conclusions: The full extent of the association between TGF-alpha overexpression and the development of SCC is unknown. Evidence is presented in this article that TGF-alpha overexpression mediates the relationship between 13-CRA and DOL, but there is no direct evidence that it mediates the relationship between 13-CRA and the prevention of SCC. Determination of the extent to which TGF-alpha overexpression mediates this relationship and complete validation of TGF-alpha's role as a surrogate endpoint biomarker await the results of animal and human trials that utilize reduction in the incidence of SCC as their endpoint. [ABSTRACT FROM AUTHOR]

BACKGROUND:Dysplastic oral leukoplakia (DOL) has been the index lesion in prevention trials for upper aerodigestive tract squamous cell carcinoma (SCC). Vitamin A derivatives, including 13-cis retinoic acid (13-CRA), have been used to treat DOL and to reduce the risk of subsequent SCC. Results from a trial of 13-CRA in patients with DOL are presented here. Transforming growth factor-α (TGF-α) and the epidermal growth factor receptor messenger RNA (mRNA) expression were studied to validate their use as surrogate endpoint biomarkers in prevention trials for SCC.STUDY DESIGN:In a prospective, randomized, double-blind trial of 13-CRA in 28 patients with DOL, TGF-α and epidermal growth factor receptor mRNA expression were analyzed in sequential biopsy specimens of DOL and of adjacent normal-appearing mucosa, utilizing a quantitative, competitive, reverse transcriptase polymerase chain reaction and were compared using the Wilcoxon signed-rank test for paired comparisons.RESULTS:In biopsy specimens of DOL, TGF-α mRNA expression at baseline, but not baseline expression of epidermal growth factor receptor mRNA, was significantly elevated when compared with its expression in specimens from adjacent normal-appearing mucosa (p = 0.003). In patients randomized to 13-CRA who had ≥ 50% clearance of DOL during treatment, significant modulation of TGF-α mRNA overexpression was seen after 6 months of treatment (p = 0.016). TGF-α mRNA overexpression at baseline predicted a subsequent response to 13-CRA (p = 0.066).CONCLUSIONS:The full extent of the association between TGF-α overexpression and the development of SCC is unknown. Evidence is presented in this article that TGF-α overexpression mediates the relationship between 13-CRA and DOL, but there is no direct evidence that it mediates the relationship between 13-CRA and the prevention of SCC. Determination of the extent to which TGF-α overexpression mediates this relationship and complete validation of TGF-α’s role as a surrogate endpoint biomarker await the results of animal and human trials that utilize reduction in the incidence of SCC as their endpoint. [ABSTRACT FROM AUTHOR]

The BAFF-APRIL system is crucial for the pathogenesis of systemic lupus erythematosus (SLE) by promoting B cell survival, differentiation and the maintenance of humoral autoimmunity. Here, we investigated the relationship of BCMA expression on B cell subsets with its ligands BAFF and APRIL, together with soluble BCMA, and with clinical and serologic variables in a cohort of 100 SLE patients (86 under conventional and 14 under belimumab therapy) and 30 healthy controls (HCs) using multicolor flow cytometry and ELISA. We found that BCMA expression in SLE patients was significantly increased on all B cell subsets compared to HCs, with all examined components of the BAFF-APRIL system being upregulated. BCMA expression was significantly increased on switched and unswitched memory B cells compared to naïve B cells, both in HCs and SLE. BCMA expression on B cells correlated with plasmablast frequencies, serum anti-dsDNA antibodies and complement consumption, while soluble BCMA correlated with plasmablast frequency, highlighting its potential as a clinical biomarker. Belimumab treatment significantly reduced BCMA expression on most B cell subsets and soluble TACI and contributed to the inhibition of almost the entire BAFF-APRIL system and restoration of B cell homeostasis. These results provide insights into the complex dysregulation of the BAFF-APRIL system in SLE and highlight the therapeutic potential of targeting its components, particularly BCMA, in addition to its use as a biomarker for disease activity. [ABSTRACT FROM AUTHOR]

A 144-day study assessed the effects of dietary energy and implant potency to determine optimum strategies for managing feed conversion (F:G) and marbling. Fifty-four Angus steers (327 ± 8 kg) from Iowa State University's herd genetically selected for enhanced marbling were stratified by initial bodyweight (BW), ultrasound intramuscular fat, and age to a 2 × 3 factorial. Dietary treatments included: low energy (1.30 Mcal NEg/kg DM, 18% roughage level; LE) or high energy finishing ration (1.39 Mcal NEg/kg DM, 8% roughage; HE). Implant treatments (IMP; Merck) included: no implant (NOIMP), Revalor-IS (RIS), or Revalor-200 (R200) on d 0 and 74. Steers were fed via bunks capturing daily individual feed disappearance (n = 9 steers/treatment). Steers were weighed on d 0, 74, and 144 and harvested on d 145. Data were analyzed in Proc Mixed of SAS with fixed effects of diet, IMP, and interaction. No interactions were observed for feedlot performance (P > 0.17). Steers fed HE had greater average daily gain (ADG) and final BW than LE steers (P < 0.01) while LE steers had greater F:G (P = 0.04). Final BW and ADG were greatest for R200, intermediate for RIS, and lowest for NOIMP (P < 0.01). F:G was greatest for NOIMP, intermediate for RIS, and lowest for R200 (P < 0.01). Steers fed HE had increased ribeye area (P < 0.01) and tended to have greater marbling score (P = 0.06; 809) than LE steers (769). While ribeye area increased in response to implant potency (P < 0.01), marbling score was not impacted (P = 0.21) by IMP (815, 771, 782, for NOIMP, RIS, R200, respectively). Overall, steers graded 100% Choice or higher and 55% Prime. These data suggest implants, when used appropriately, improve growth performance and efficiency in beef steers without compromising carcass quality. [ABSTRACT FROM AUTHOR]

This study assessed the effect of Sweet BranTM (SWBR; 40% DM inclusion; Cargill Corn Milling, Blair, NE) or modified distiller's grains (MDGS; 25% DM inclusion) in the diet of newly received feedlot steers on feeding behavior and growing period performance. Diets were formulated for similar metabolizable protein and DM. Two hundred sixteen freshly weaned Angus-cross steers (253 kg ± 18.1) were stratified by BW to 36 pens (n = 18 per treatment; 6 steers/pen). Individual BW were recorded on d 0, 28, and 60. Eight pens per treatment were utilized to assess rate of feed disappearance early (day 5 and 6) and late (53 and 54) during growing by weighing feed in bunks every 2 hours post-delivery for 12 consecutive hours. Feed weights were averaged across consecutive days within pen and timepoint. Slopes were calculated between each timepoint to determine rate of feed disappearance. Data were analyzed with Proc Mixed of SAS 9.4; diet was fixed effect and pen was experimental unit. Feed disappearance slopes were analyzed as repeated measures with the repeated effect of time. Body weights did not differ on d 28 (P ≥ 0.29), but d 60 BW and d 0 to 60 ADG were greater for SWBR than MDGS (P < 0.05). Steers fed SWBR had greater DMI throughout the trial (P < 0.05). Feed efficiency (G:F) did not differ throughout the trial (P ≥ 0.31). Rate of feed disappearance on d 5/6 was greater for SWBR between hours 6-8, and greater for MDGS from hours 10-12. On d 53/54, SWBR had increased feeding rate during hours 0-2, while MDGS was increased from hours 8-10. Steers fed SWBR had a greater rate of feed disappearance earlier in the day and had improved DMI and growth than steers fed MDGS. [ABSTRACT FROM AUTHOR]