bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal diffusion tensor imaging in frontotemporal dementia
Authors: Mahoney Colin J. , Simpson Ivor J. A. , Nicholas Jennifer M. , Fletcher Phillip D. , Downey Laura E. , Golden Hannah L. , Clark Camilla N. , Schmitz Nicole , Rohrer Jonathan D. , Schott Jonathan M. , Zhang Hui , Ourselin Sebastian , Warren Jason D. , Fox Nick C. 
Published: November 2014

ObjectiveNovel biomarkers for monitoring progression in neurodegenerative conditions are needed. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. Here we report trajectories of WM change using serial DTI in a cohort with behavioral variant frontotemporal dementia (bvFTD).MethodsTwenty‐three patients with bvFTD (12 having genetic mutations), and 18 age‐matched control participants were assessed using DTI and neuropsychological batteries at baseline and ∼1.3 years later. Baseline and follow‐up DTI scans were registered using a groupwise approach. Annualized rates of change for DTI metrics, neuropsychological measures, and whole brain volume were calculated. DTI metric performances were compared, and sample sizes for potential clinical trials were calculated.ResultsIn the bvFTD group as a whole, rates of change in fractional anisotropy (FA) and mean diffusivity (MD) within the right paracallosal cingulum were greatest (FA: −6.8%/yr, p < 0.001; MD: 2.9%/yr, p = 0.01). MAPT carriers had the greatest change within left uncinate fasciculus (FA: −7.9%/yr, p < 0.001; MD: 10.9%/yr, p < 0.001); sporadic bvFTD and C9ORF72 carriers had the greatest change within right paracallosal cingulum (sporadic bvFTD, FA: −6.7%/yr, p < 0.001; MD: 3.8%/yr, p = 0.001; C9ORF72, FA: −6.8%/yr, p = 0.004). Sample size estimates using FA change were substantially lower than neuropsychological or whole brain measures of change.InterpretationSerial DTI scans may be useful for measuring disease progression in bvFTD, with particular trajectories of WM damage emerging. Sample size calculations suggest that longitudinal DTI may be a useful biomarker in future clinical trials. ANN NEUROL 2015;77:33–46
Controlled dispersion of a porphyrin/fullerene donor‐acceptor complex in semiconducting polymer thin films: Intermolecular interactions of polymers with porphyrin and fullerene
Authors: Natori Itaru , Natori Shizue , Hanawa Naoki , Ogino Kenji 
Published: November 2014

ABSTRACTThin films composed of semiconducting polymers [poly(2‐vinyl naphthalene), poly(4‐diphenyl aminostyrene), poly(1‐vinyl pyrene), and poly(3‐hexyl thiophene‐2,5‐diyl)], zinc(II)−5,10,15,20‐tetra‐(2‐naphthyl)porphyrin, and [6,6]‐phenyl‐C61‐butyric acid methyl ester blends were prepared to investigate the controlled dispersion of porphyrin molecules in semiconducting polymer thin films. Tailoring the intermolecular interactions between the polymer/fullerene, polymer/porphyrin, and porphyrin/fullerene systems was found to be an effective method of controlling the dispersion. When the polymer/porphyrin interactions were enhanced, intermixed porphyrin/fullerene donor–acceptor complex domains were formed, whereas under conditions where the polymer/porphyrin interactions were weakened, the complex assembled at the borders between the polymer and fullerene phases. This concept could potentially be applied to various combinations of porphyrin/fullerene systems in semiconducting polymer thin films to develop polymer solar cells with excellent performance. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41629.
Essential dynamics analysis captures the concerted motion of the integrin‐binding site in jerdostatin, an RTS disintegrin
Authors: Calvanese Luisa , Falcigno Lucia , D'Auria Gabriella 
Published: November 2014

ABSTRACTDisintegrins, small molecular weight proteins contained in the venom of vipers and rattlesnakes, are high‐affinity and selectivity integrin antagonists. Disintegrins inhibitory epitope mainly consists in a tripeptide sequence localized in a mobile loop protruding from the protein core. RTS and/or KTS tripeptide characterizes the most recently discovered group of disintegrins that selectively block α1β1 integrin receptor. A NMR study dedicated to structure and dynamics properties of jerdostatin, an RTS disintegrin, demonstrated that the substitution of the native RTS with KTS motif impaired flexibility and inhibitory activity of the molecule. Here we add atomic details to the experimental profiles of jerdostatin and its R24K mutant by analyzing the dynamics behavior of the molecules through computational methods. For jerdostatin wild type, molecular dynamics simulations and essential dynamics analyses showed that Y31 residue acts as hinge element in the concerted motions involving the active loop and the C‐terminal tail. R24 side chain ability to engage both cation–π and H‐bond interactions with Y31 residue was found crucial for that breathing mechanism. Less significant loop‐tail concerted motions were observed for the R24K mutant. The description at atomic resolution of jerdostatin dynamics is useful for decoding the influence of specific residues on disintegrin functional properties. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 158–166, 2015.
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives
Authors: Serrano Isa D. , Ramu Vasanthakumar G. , Pinto Antónia R. T. , Freire João M. , Tavares Isaura , Heras Montserrat , Bardaji Eduard R. , Castanho Miguel A. R. B. 
Published: November 2014

ABSTRACTAmidated kyotorphin (l‐Tyr‐l‐Arg‐NH2; KTP‐NH2) causes analgesia when systemically administered. The lipophilic ibuprofen‐conjugated derivative of KTP‐NH2 has improved analgesic efficacy. However, fast degradation by peptidases impacts negatively in the pharmacodynamics of these drugs. In this work, selected derivatives of KTP and KTP‐NH2 were synthesized to combine lipophilicity and resistance to enzymatic degradation. Eight novel structural modifications were tested for the potential to transverse lipid membranes and to evaluate their efficacy in vivo. The rationale behind the design of the pool of the eight selected molecules consisted in the addition of individual group at the N‐terminus, namely the tert‐butyloxycarbonyl (Boc), γ‐aminobutyric acid (GABA), acetyl, butanoyl, and propanoyl or in the substitution of the tyrosine residue by an indole moiety and in the replacement of the peptidic bond by a urea‐like bond in some cases. All the drugs used in the study are intrinsically fluorescent, which enables the use of spectrofluorimetry to sample the drugs in the permeation assays. The results show that the BOC and indolyl derivatives of KTP‐NH2 have maximal ability to permeate membranes with concomitant maximal analgesic power. Overall, the results demonstrate that membrane permeation is correlated with analgesic efficacy. However, this is not the only factor accounting for analgesia. KTP‐NH2 for instance has low passive permeation but is known to have central action. In this case, hypothetical transcytosis over the blood‐brain barrier seems to depend on dipeptide transporters. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 1–10, 2015.
Beaded nanofibers assembled from double‐hydrophobic elastin‐like block polypeptides: Effects of trifluoroethanol
Authors: Le Duc H. T. , Okubo Tatsuya , Sugawara‐Narutaki Ayae 
Published: November 2014

AbstractA “double‐hydrophobic” elastin‐like triblock polypeptide GPG has been constructed by mimicking the localization of proline‐ and glycine‐rich hydrophobic domains of native elastin, a protein that provides elasticity and resilience to connective tissues. In this study, the effects of trifluoroethanol (TFE), an organic solvent that strongly affects secondary structures of polypeptides on self‐assembly of GPG in aqueous solutions were systematically studied. Beaded nanofiber formation of GPG, where nanoparticles are initially formed by coacervation of the polypeptides followed by their connection into one‐dimensional nanostructures, is accelerated by the addition of TFE at the concentrations up to 30% (v/v), whereas aggregates of nanoparticles are formed at 60% TFE. The concentration‐dependent assembly pattern discussed is based on the influence of TFE on the secondary structures of GPG. Well‐defined nanofibers whose diameter and secondary structures are controlled by TFE concentration may be ideal building blocks for constructing bioelastic materials in tissue engineering. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 175–185, 2015.
The structure and mechanical properties of the proteins of lamprey cartilage
Authors: Green Ellen M. , Peter Winlove C. 
Published: November 2014

ABSTRACTThe cyanogen bromide‐resistant proteins of lamprey cartilage are biochemically related to the mammalian elastic protein, elastin. This study investigates their mechanical properties and enquires whether, like elastin, long‐range elasticity arises in them from a combination of entropic and hydrophobic mechanisms. Branchial and pericardial proteins resembled elastin mechanically, with elastic moduli of 0.13–0.35 MPa, breaking strains of 50%, and low hysteresis. Annular and piston proteins had higher elastic moduli (0.27–0.75 MPa) and larger hysteresis. Exchanging solvent water for trifluoroethanol increased the elastic moduli, whereas increasing temperature lowered the elastic moduli. Raman microspectrometry showed small differences in side‐chain modes consistent with reported biochemical differences. Decomposition of the amide I band indicated that the secondary structures were like those of elastin, preponderantly unordered, which probably confer the conformational flexibility necessary for entropy elasticity. Piston and annular proteins showed the strongest interactions with water, suggesting, together with the mechanical testing data, a greater role of hydrophobic interactions in their mechanics. Two‐photon imaging of intrinsic fluorescence and dye injection experiments showed that annular and piston proteins formed closed‐cell honeycomb structures, whereas the branchial and pericardial proteins formed open‐cell structures, which may account for the differences in mechanical properties. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 187–202, 2015.
Engineering cellular redox balance in Saccharomyces cerevisiae for improved production of L‐lactic acid
Authors: Lee Ju Young , Kang Chang Duk , Lee Seung Hyun , Park Young Kyoung , Cho Kwang Myung 
Published: November 2014

ABSTRACTOwing to the growing market for the biodegradable and renewable polymer, polylactic acid, world demand for lactic acid is rapidly increasing. However, the very high concentrations desired for industrial production of the free lactic acid create toxicity and low pH concerns for manufacturers. Saccharomyces cerevisiae is the most well characterized eukaryote, a preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust, commercially compatible workhorse to be exploited for the production of diverse chemicals. S. cerevisiae has also been explored as a host for lactic acid production because of its high acid tolerance. Here, we constructed an L‐lactic acid‐overproducing S. cerevisiae by redirecting cellular metabolic fluxes to the production of L‐lactic acid. To this end, we deleted the S. cerevisiae genes encoding pyruvate decarboxylase 1 (PDC1), L‐lactate cytochrome‐c oxidoreductase (CYB2), and glycerol‐3‐phosphate dehydrogenase (GPD1), replacing them with a heterologous L‐lactate dehydrogenase (LDH) gene. Two new target genes encoding isoenzymes of the external NADH dehydrogenase (NDE1 and NDE2), were also deleted from the genome to re‐engineer the intracellular redox balance. The resulting strain was found to produce L‐lactic acid more efficiently (32.6% increase in final L‐lactic acid titer). When tested in a bioreactor in fed‐batch mode, this engineered strain produced 117 g/L of L‐lactic acid under low pH conditions. This result demonstrates that the redox balance engineering should be coupled with the metabolic engineering in the construction of L‐lactic acid‐overproducing S. cerevisiae. Biotechnol. Bioeng. 2015;112: 751–758. © 2014 Wiley Periodicals, Inc.
Metabolic process engineering of Clostridium tyrobutyricum Δack–adhE2 for enhanced n‐butanol production from glucose: Effects of methyl viologen on NADH availability, flux distribution, and fermentation kinetics
Authors: Du Yinming , Jiang Wenyan , Yu Mingrui , Tang I‐Ching , Yang Shang‐Tian 
Published: November 2014

ABSTRACTButanol biosynthesis through aldehyde/alcohol dehydrogenase (adhE2) is usually limited by NADH availability, resulting in low butanol titer, yield, and productivity. To alleviate this limitation and improve n‐butanol production by Clostridium tyrobutyricum Δack–adhE2 overexpressing adhE2, the NADH availability was increased by using methyl viologen (MV) as an artificial electron carrier to divert electrons from ferredoxin normally used for H2 production. In the batch fermentation with the addition of 500 μM MV, H2, acetate, and butyrate production was reduced by more than 80–90%, while butanol production increased more than 40% to 14.5 g/L. Metabolic flux analysis revealed that butanol production increased in the fermentation with MV because of increased NADH availability as a result of reduced H2 production. Furthermore, continuous butanol production of ∼55 g/L with a high yield of ∼0.33 g/g glucose and extremely low ethanol, acetate, and butyrate production was obtained in fed‐batch fermentation with gas stripping for in situ butanol recovery. This study demonstrated a stable and reliable process for high‐yield and high‐titer n‐butanol production by metabolically engineered C. tyrobutyricum by applying MV as an electron carrier to increase butanol biosynthesis. Biotechnol. Bioeng. 2015;112: 705–715. © 2014 Wiley Periodicals, Inc.
Highly efficient targeted chromosome deletions using CRISPR/Cas9
Authors: He Zuyong , Proudfoot Chris , Mileham Alan J. , McLaren David G. , Whitelaw C. Bruce A. , Lillico Simon G. 
Published: November 2014

ABSTRACTThe CRISPR/Cas9 system has emerged as an intriguing new technology for genome engineering. It utilizes the bacterial endonuclease Cas9 which, when delivered to eukaryotic cells in conjunction with a user‐specified small guide RNA (gRNA), cleaves the chromosomal DNA at the target site. Here we show that concurrent delivery of gRNAs designed to target two different sites in a human chromosome introduce DNA double‐strand breaks in the chromosome and give rise to targeted deletions of the intervening genomic segment. Predetermined genomic DNA segments ranging from several‐hundred base pairs to 1 Mbp can be precisely deleted at frequencies of 1–10%, with no apparent correlation between the size of the deleted fragment and the deletion frequency. The high efficiency of this technique holds promise for large genomic deletions that could be useful in generation of cell and animal models with engineered chromosomes. Biotechnol. Bioeng. 2015;112: 1060–1064. © 2014 Wiley Periodicals, Inc.
Advanced tools for fluid and fouling layer characterization applied to the description of membrane fouling phenomena for particle‐organic matter mixtures
Authors: Loulergue Patrick , Teychene Benoit , Weckert Marie , Cabassud Corinne , Guigui Christelle 
Published: November 2014

AbstractFouling by the formation of a complex cake remains a major hindrance of membrane bioreactors. One approach to fouling mitigation is to add particles within the biofluid in order to improve sludge filterability. Despite a number of studies dealing with this topic, fouling mechanisms are still not clear. This study reports the use of an original methodology for better fouling understanding and mitigation. This original approach is based on in situ characterization of cake local structural properties together with a detailed fluid characterization using size exclusion chromatography and the monitoring of global filtration performances.In order to obtain comprehensive elements, the impact of particle addition within cakes having markedly different behaviours (slightly and highly compressible cake, different specific resistance) was investigated considering different biofluids and membranes. The results demonstrated that a potential beneficial effect of particles on filtration performance depended on the cake properties in the absence of particles. It was found that particle addition could only improve biofluid filterability when the fouling layer was highly compressible and consisted mainly of macromolecular protein. In addition, in situ characterization revealed that particles within the fouling layer strongly influenced organic matter deposition at the membrane. It also showed that the effect of particles on fouling mitigation depended on the environment surrounding them within the fouling layer.
Sox5 controls dorsal progenitor and interneuron specification in the spinal cord
Authors: Quiroga Alejandra C. , Stolt C. Claus , del Corral Ruth Diez , Dimitrov Spas , Pérez‐Alcalá Siro , Sock Elisabeth , Barbas Julio A. , Wegner Michael , Morales Aixa V. 
Published: November 2014

ABSTRACTThe basic organization of somatosensory circuits in the spinal cord is already setup during the initial patterning of the dorsal neural tube. Extrinsic signals, such as Wnt and TGF‐β pathways, activate combinatorial codes of transcription factors that are responsible for generating a pattern of discrete domains of dorsal progenitors (dp). These progenitors will give rise to distinct dorsal interneurons (dI). The Wnt/ βcatenin signaling pathway controls specification of dp/dI1–3 progenitors and interneurons. According to the current model in the field, Wnt/βcatenin activity seems to act in a graded fashion in the spinal cord, as different relative levels determine the identity of adjacent progenitors. However, it is not clear how this activity gradient is controlled and how the identities of dI1–3 are differentially regulated by Wnt signalling. We have determined that two SoxD transcription factors, Sox5 and Sox6, are expressed in restricted domains of dorsal progenitors in the neural tube. Using gain‐ and loss‐of function approaches in chicken embryos, we have established that Sox5 controls cell fate specification of dp2 and dp3 progenitors and, as a result, controls the correct number of the corresponding dorsal interneurons (dI2 and dI3). Furthermore, Sox5 exerts its function by restricting dorsally Wnt signaling activity via direct transcriptional induction of the negative Wnt pathway regulator Axin2. By that way, Sox5 acts as a Wnt pathway modulator that contributes to sharpen the dorsal gradient of Wnt/βcatenin activity to control the distinction of two functionally distinct types of interneurons, dI2 and dI3 involved in the somatosensory relay. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 522–538, 2015
Differential regulation of Hes/Hey genes during inner ear development
Authors: Petrovic Jelena , Gálvez Hector , Neves Joana , Abelló Gina , Giraldez Fernando 
Published: November 2014

ABSTRACTNotch signaling plays a crucial role during inner ear development and regeneration. Hes/Hey genes encode for bHLH transcription factors identified as Notch targets. We have studied the expression and regulation of Hes/Hey genes during inner ear development in the chicken embryo. Among several Hes/Hey genes examined, only Hey1 and Hes5 map to the sensory regions, although with salient differences. Hey1 expression follows Jag1 expression except at early prosensory stages while Hes5 expression corresponds well to Dl1 expression throughout otic development. Although Hey1 and Hes5 are direct Notch downstream targets, they differ in the level of Notch required for activation. Moreover, they also differ in mRNA stability, showing different temporal decays after Notch blockade. In addition, Bmp, Wnt and Fgf pathways also modify Hey1 and Hes5 expression in the inner ear. Particularly, the Wnt pathway modulates Hey1 and Jag1 expression. Finally, gain of function experiments show that Hey1 and Hes5 cross‐regulate each other in a complex manner. Both Hey1 and Hes5 repress Dl1 and Hes5 expression, suggesting that they prevent the transition to differentiation stages, probably by preventing Atoh1 expression. In spite of its association with Jag1, Hey1 does not seem to be instrumental for lateral induction as it does not promote Jag1 expression. We suggest that, besides being both targets of Notch, Hey1 and Hes5 are subject to a rather complex regulation that includes the stability of their transcripts, cross regulation and other signaling pathways. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 703–720, 2015
Characteristics associated with clinician diagnosis of aspiration pneumonia: A descriptive study of afflicted patients and their outcomes
Authors: Lanspa Michael J. , Peyrani Paula , Wiemken Timothy , Wilson Emily L. , Ramirez Julio A. , Dean Nathan C. 
Published: November 2014

BACKGROUNDAspiration pneumonia is a common disease, although less well characterized than other pneumonia syndromes.OBJECTIVEWe analyzed patient‐level covariates associated with clinician‐defined aspiration pneumonia.METHODSWe used the Community‐Acquired Pneumonia Organization database, a multicenter, international population of patients with community‐acquired pneumonia, using data from 2001 to 2012. Aspiration pneumonia was determined by the treating clinician. We analyzed covariates associated with clinician‐defined diagnosis of aspiration pneumonia using logistic regression. We compared aspiration pneumonia patients to propensity‐matched cases with nonaspiration pneumonia.RESULTSWe studied 5185 patients. Four hundred fifty‐one of these patients had aspiration pneumonia. Patients with aspiration pneumonia were older, had greater disease severity, and more comorbidities than patients with nonaspiration pneumonia. They were more likely cared for in the intensive care unit (19% vs 13%, P = 0.002), had longer unadjusted hospital length of stay (9 vs 7 days, P < 0.001), and took longer to achieve clinical stability (unadjusted 8 vs 4 days, P < 0.001). Confusion, nursing home residence, and cerebrovascular disease were most associated with clinician diagnosis of aspiration pneumonia (odds ratio: 4.4, 2.9, 2.3, respectively). Unadjusted inpatient mortality was higher (23% vs 9%, P < 0.001). Aspiration pneumonia conferred a 2.3 odds ratio for inpatient mortality after adjusting for age, disease severity, and comorbidities.CONCLUSIONSAmong pneumonia patients, confusion, nursing home residence, and cerebrovascular disease are associated with a clinician diagnosis of aspiration. Aspiration pneumonia is associated with greater mortality among patients with community‐acquired pneumonia, which is not explained by older age, measured indices of severity, or comorbidities. Journal of Hospital Medicine 2015;10:90–96. © 2014 Society of Hospital Medicine