bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformational selection and adaptation to ligand binding in T4 lysozyme cavity mutants
Authors: López Carlos J. , Yang Zhongyu , Altenbach Christian , Hubbell Wayne L. 
Published: October 2013

Significance
Analysis of protein packing reveals the prevalence of cavities, some of which are evolutionarily conserved. Despite the fact that these packing defects are generally destabilizing, they can play important roles in facilitating functionally important protein motions and in the evolution of protein function. In this study, we used site-directed spin-labeling with electron paramagnetic resonance spectroscopy to investigate the structural and dynamical response of an enzyme to engineered ligand-binding cavities. The results show that the engineered cavities introduce conformational fluctuations between a native-like state and a new state. Ligand binding shifts the equilibrium toward the native-like state, suggesting binding via conformational selection, although additional structural adaptation is observed for one mutant. The results underscore the potential role of cavities in modulating molecular flexibility.
Fast protein fragment similarity scoring using a Binet–Cauchy kernel
Authors: Guyon Frédéric , Tufféry Pierre 
Published: October 2013

Abstract
Motivation: Meaningful scores to assess protein structure similarity are essential to decipher protein structure and sequence evolution. The mining of the increasing number of protein structures requires fast and accurate similarity measures with statistical significance. Whereas numerous approaches have been proposed for protein domains as a whole, the focus is progressively moving to a more local level of structure analysis for which similarity measurement still remains without any satisfactory answer.
Results: We introduce a new score based on Binet–Cauchy kernel. It is normalized and bounded between 1—maximal similarity that implies exactly the same conformations for protein fragments—and −1—mirror image conformations, the unrelated conformations having a null mean score. This allows for the search of both similar and mirror conformations. In addition, such score addresses two major issue of the widely used root mean square deviation (RMSD). First, it achieves length independent statistics even for short fragments. Second, it shows better performance in the discrimination of medium range RMSD values. Being simpler and faster to compute than the RMSD, it also provides the means for large-scale mining of protein structures.
Availability and implementation: The computer software implementing the score is available at http://bioserv.rpbs.univ-paris-diderot.fr/BCscore/
Contact: frederic.guyon@univ-paris-diderot.fr
Supplementary Information: Supplementary data are available at Bioinformatics online.
Daptomycin‐Loaded Polymethylmethacrylate Bone Cement for Joint Arthroplasty Surgery
Authors: Hsu Yuan‐Ming , Liao Chun‐Hsing , Wei Yu‐Hong , Fang Hsu‐Wei , Hou Hsiang‐Huan , Chen Chia‐Chun , Chang Chih‐Hung 
Published: October 2013

AbstractAntibiotic‐loaded acrylic bone cement has been frequently used as an infection prophylaxis or antibiotic‐loaded spacer in infected arthroplasty. In addition, daptomycin has been used recently against broad spectrum Gram‐positive organisms. The goal of this in vitro study is to investigate the bacteriacidal and mechanical properties of daptomycin‐incorporated polymethylmethacrylate (PMMA) bone cement and evaluate its feasibility for clinical use. Daptomycin (0.5, 1, or 2 g) was premixed with 40 g of PMMA bone cement powder before curing. The mechanical properties of the daptomycin‐loaded acrylic bone cement (DLABC) were estimated following standard guidance, and the release profile and kinetics of daptomycin from PMMA were analyzed. The antimicrobial efficacy of DLABC was determined with a zone of inhibition (ZOI) assay against Staphylococcus aureus, Staphylococcus epidermis, Enterococcus faecalis, and Enterococcus faecium, respectively. The results showed that the compressive strength, of PMMA bone cement, which was higher than 100 MPa in all groups, was sufficient according to ISO 5833 after incorporation of daptomycin. The encapsulated daptomycin was released for 2 weeks with a 9.59 ± 0.85%, 15.25 ± 0.69%, and 20.64 ± 20.33% released percentage on the first day in the low, mid, and high groups, respectively. According to the calculated release kinetics, incorporated daptomycin should be 3.3 times the original dose to double its release. Although all recipes of DLABC had a microbial inhibitory effect, the effect with a higher encapsulated amount of daptomycin was more significant. Therefore, we believe that daptomycin can be locally delivered from PMMA bone cement at the surgical site as a prophylactic or treatment for osteomyelitis against Gram‐positive organisms with intact cement function.
Induction of apoptosis and G2/M cell cycle arrest by Scrophularia striata in a human leukaemia cell line
Authors: Azadmehr A. , Hajiaghaee R. , Mazandarani M. 
Published: October 2013

AbstractObjectivesScrophularia striata Boiss (Scrophulariaceae) is a plant that grows in northeastern Iran; it has been used traditionally to treat various inflammatory disorders. This study was designed to investigate cytotoxic effects of S. striata extract, on the Jurkat human leukaemia cell line (T‐cell leukaemia).Materials and methodsPhytochemical assay by thin layer chromatography and 2, 2 diphenyl‐1‐picryl‐hydrazyl were used to evaluate main compounds and antioxidant capacity of the plant extract, respectively. Its inhibitory effect on Jurkat cells was evaluated by MTT assay. In addition, cell cycle distribution and apoptotic cell death were evaluated by propidium iodide and annexin V‐FITC/ propidium iodide staining.ResultsThese showed that the main components present in S. striata extract included flavonoids, phenolic compounds and phenyl propanoids. Treatment with extract was significantly cytotoxic to the tumour cell line. In addition, flow cytometry analysis indicated that S. striata extract induced cell cycle arrest in G2/M phase and apoptosis of tumour cells.ConclusionsResults of the study indicated that S. striata extract could inhibit leukaemia cell proliferation by inducing G2/M phase arrest and apoptosis.
Use of Groundwater Levels with the PULSE Analytical Model
Authors: Rutledge Albert T. 
Published: October 2013

AbstractThe PULSE analytical model, which calculates daily groundwater discharge on the basis of user‐specified recharge, was originally developed for calibration using streamflow data. This article describes a model application in which groundwater level data constitute the primary control on model input. As a test case, data were analyzed from a small basin in central Pennsylvania in which extensive groundwater level data are available. The timing and intensity of daily water‐level rises are used to ascertain temporal distribution of recharge, and the simulated groundwater discharge hydrograph has shape features that are similar to the streamflow hydrograph. This article does not include details about calibration, but some steps are illustrated and general procedures are described for calibration in specific hydrologic studies. The PULSE model can be used to assess results of fully automated base flow methods and can be used to define groundwater recharge and discharge at a relatively small time scale.
Pityriasis rubra pilaris: clinicopathological study of 32 cases from Lebanon
Authors: Marrouche Nadine , Kurban Mazen , Kibbi Abdul‐Ghani , Abbas Ossama 
Published: October 2013

SummaryBackgroundPityriasis rubra pilaris (PRP) is an uncommon papulosquamous disorder of unknown etiology. Studies on this condition from our region are lacking.MethodsTo describe the clinical and histopathological findings as well as response to treatment of all patients diagnosed with PRP at the American University of Beirut Medical Center between 1995 and 2010 and compare our findings with those published in the literature.ResultsPityriasis rubra pilaris was diagnosed in 32 patients (16 males, 16 females). Age of onset ranged between 2.5 and 70 years. The majority of patients (n = 15) were classified as type I (47%) followed by type III (n = 9, 28%) and type IV (n = 6, 19%). Based on treatment responses, retinoids appear to be very effective in our population as all patients treated with isotretinoin or acitretin had excellent response. In addition to checkerboard alternating orthokeratosis/parakeratosis, which was observed in 31 cases, interesting features, including the presence of follicular plugging in all 21 cases in which follicles were available for examination, eosinophils in 12 cases, and focal acantholysis in three cases were observed.ConclusionsFeatures of patients with PRP in our study are generally comparable to those published in the literature, with minor differences. Microscopically follicular plugging, in addition to checkerboard alternating orthokeratosis/parakeratosis, may serve as clues to PRP diagnosis. The presence of eosinophils and focal acantholysis, observed in a few cases, should not exclude PRP diagnosis.
Communication, Excess Comovement and Factor Structures
Authors: Yang Baozhong 
Published: October 2013

AbstractThis paper develops a model in which investors communicate before trading in a general equilibrium. Investors repeatedly communicate in a social network but have limited knowledge of the network structure and thus do not fully realize the consequences of their communication and belief updating. As a result, asset returns contain excess comovement and more concentrated factor structures than fundamental values do. The model generates testable empirical predictions that are consistent with the empirical literature on excess comovement in asset returns.
A single amino acid residue controls ROS production in the respiratory Complex I from Escherichia coli
Authors: Knuuti Juho , Belevich Galina , Sharma Vivek , Bloch Dmitry A. , Verkhovskaya Marina 
Published: October 2013

SummaryReactive oxygen species (ROS) production by respiratory Complex I from Escherichia coli was studied in bacterial membrane fragments and in the isolated and purified enzyme, either solubilized or incorporated in proteoliposomes. We found that the replacement of a single amino acid residue in close proximity to the nicotinamide adenine dinucleotide (NADH)‐binding catalytic site (E95 in the NuoF subunit) dramatically increases the reactivity of Complex I towards dioxygen (O2). In the E95Q variant short‐chain ubiquinones exhibit strong artificial one‐electron reduction at the catalytic site, also leading to a stronger increase in ROS production. Two mechanisms can contribute to the observed kinetic effects: (a) a change in the reactivity of flavin mononucleotide (FMN) towards dioxygen at the catalytic site, and (b) a change in the population of the ROS‐generating state. We propose the existence of two (closed and open) states of the NAD+‐bound enzyme as one feature of the substrate‐binding site of Complex I. The analysis of the kinetic model of ROS production allowed us to propose that the population of Complex I with reduced FMN is always low in the wild‐type enzyme even at low ambient redox potentials, minimizing the rate of reaction with O2 in contrast to E95Q variant.
Theoretical Study of the Reaction Formalhydrazone with Singlet Oxygen. Fragmentation of the C=N Bond, Ene Reaction and Other Processes
Authors: Rudshteyn Benjamin , Castillo Álvaro , Ghogare Ashwini A. , Liebman Joel F. , Greer Alexander 
Published: October 2013

AbstractPhotobiologic and synthetic versatility of hydrazones has not yet been established with 1O2 as a route to commonly encountered nitrosamines. Thus, to determine whether the “parent” reaction of formalhydrazone and 1O2 leads to facile C=N bond cleavage and resulting nitrosamine formation, we have carried out CCSD(T)//DFT calculations and analyzed the energetics of the oxidation pathways. A [2 + 2] pathway occurs via diradicals and formation of 3‐amino‐1,2,3‐dioxazetidine in a 16 kcal/mol−1 process. Reversible addition or physical quenching of 1O2 occurs either on the formalhydrazone carbon for triplet diradicals at 2–3 kcal mol−1, or on the nitrogen (N(3)) atom forming zwitterions at ~15 kcal/mol−1, although the quenching channel by charge‐transfer interaction was not computed. The computations also predict a facile conversion of formalhydrazone and 1O2 to hydroperoxymethyl diazene in a low‐barrier ‘ene’ process, but no 2‐amino‐oxaziridine‐O‐oxide (perepoxide‐like) intermediate was found. A Benson‐like analysis (group increment calculations) on the closed‐shell species are in accord with the quantum chemical results.
Low but Sufficient Anidulafungin Exposure in Critically Ill Patients
Authors: van Wanrooy Marjolijn J. P. , Rodgers Michael G. G. , Uges Donald R. A. , Arends Jan P. , Zijlstra Jan G. , van der Werf Tjip S. , Kosterink Jos G. W. , Alffenaar Jan-Willem C. 
Published: October 2013

ABSTRACT

The efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Patients in intensive care may be at risk for underexposure. In critically ill patients with an invasive
Candida
infection, the anidulafungin exposure and a possible correlation with disease severity or plasma protein levels were explored. Concentration-time curves were therefore obtained at steady state. Anidulafungin concentrations were measured with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The MIC values of the
Candida
species were determined with the Etest. The target AUC/MIC ratio was based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) data. Twenty patients were included. The patients received a maintenance dose of 100 mg once daily after a loading dose of 200 mg on the first day. The mean (±standard deviation) AUC, maximum concentration of drug in plasma (
C
max
), and minimum concentration of drug in plasma (
C
min
) were 69.8 ± 24.1 mg · h/liter, 4.7 ± 1.4 mg/liter, and 2.2 ± 0.8 mg/liter, respectively. The MIC values of all cultured
Candida
species were below the EUCAST MIC breakpoints. The exposure to anidulafungin in relation to the MIC that was determined appeared sufficient in all patients. The anidulafungin exposure was low in our critically ill patients. However, combined with the low MICs of the isolated
Candida
strains, the lower exposure observed in comparison to the exposure in the general patient population resulted in favorable AUC/MIC ratios, based on EUCAST data. No correlation was observed between anidulafungin exposure and disease severity or plasma protein concentrations. In patients with less-susceptible
Candida albicans
or
glabrata
strains, we recommend considering determining the anidulafungin exposure to ensure adequate exposure. (This trial has been registered at ClinicalTrials.gov under registration no. NCT01047267.)
Ferric Uptake Regulator-Dependent Antinitrosative Defenses in Salmonella enterica Serovar Typhimurium Pathogenesis
Authors: Husain Maroof , Jones-Carson Jessica , Liu Lin , Song Miryoung , Saah J. Royden , Troxell Bryan , Mendoza Mary , Hassan Hosni , Vázquez-Torres Andrés 
Published: October 2013

ABSTRACT

Herein we report an important role for the ferric uptake regulator (Fur) in the resistance of
Salmonella
enterica
serovar Typhimurium to the reactive nitrogen species produced by inducible nitric oxide (NO) synthase in an NRAMP1
r
murine model of acute systemic infection. The expression of
fur
protected
Salmonella
grown under normoxic and hypoxic conditions against the bacteriostatic activity of NO. The hypersusceptibility of
fur
-deficient
Salmonella
to the cytotoxic actions of NO coincides with a marked repression of respiratory activity and the reduced ability of the bacteria to detoxify NO. A
fur
mutant
Salmonella
strain contained reduced levels of the terminal quinol oxidases of the electron transport chain. Addition of the heme precursor δ-aminolevulinic acid restored the cytochrome content, respiratory activity, NO consumption, and wild-type growth in bacteria undergoing nitrosative stress. The innate antinitrosative defenses regulated by Fur added to the adaptive response associated with the NO-detoxifying activity of the flavohemoprotein Hmp. Our investigations indicate that, in addition to playing a critical role in iron homeostasis, Fur is an important antinitrosative determinant of
Salmonella
pathogenesis.
Oxford and the Savannah: Can the Hippo Provide an Explanation for Peto's Paradox?
Authors: Kelleher Fergal C. , O'Sullivan Hazel 
Published: October 2013

Abstract
Peto's paradox is the counterintuitive finding that increasing body mass and thereby cell number does not correlate with an increase in cancer incidence across different species. The Hippo signaling pathway is an evolutionarily conserved system that determines organ size by regulating apoptosis and cell proliferation. It also affects cell growth by microRNA-29 (miR-29)–mediated cross-talk to the mTOR signaling pathway. Whether these pathways that decide organ size could explain this paradox merits consideration. Inactivation of most genes of the Hippo pathway in Drosophila melanogaster genetic screens causes excessive tissue-specific growth of developing tissues. Altered Hippo pathway activity is frequently found in diverse tumor types, but mutations of component pathway genes are rare. Most Hippo pathway components are encoded by tumor suppressor genes (TSG), but an exception is the downstream effector gene called YAP. Activity of the Hippo pathway causes deactivating phosphorylation of YES-associated protein (YAP) with nuclear exclusion. YAP can also be phosphorylated at a second site, S127, by AKT. YAP induces the expression of genes responsible for proliferation and suppression of apoptosis. Resolving Peto's paradox may serendipitously provide new insights into the biology and treatment of cancer. This article considers Hippo signaling and Peto's paradox in the context of TSG–oncogene computed models. Interspecies differences in dietary composition, metabolic rates, and anabolic processes are also discussed in the context of Hippo–mTOR signaling. The metabolically important LKB1-AMPK (liver kinase B1-AMP activated protein kinase) signaling axis that suppresses the mTOR pathway is also considered. Clin Cancer Res; 20(3); 557–64. ©2013 AACR.
Intraperitoneal chemotherapy: Rationale, applications, and limitations
Authors: Al-Quteimat Osama M , Al-Badaineh Mariam A 
Published: October 2013

Intraperitoneal chemotherapy, involving the administration of certain chemotherapeutic agents directly to the intraperitoneal cavity, was developed as a novel therapeutic strategy early in the 1950s. Intraperitoneal administration of chemotherapy results in higher intraperitoneal concentration of the cytotoxic medications and minimal systemic exposure than observed with intravenous administration, which in turn may increase the efficacy of these agents with substantial reduction in systemic toxicity. Intraperitoneal chemotherapy was used successfully in peritoneal surface malignancies, including malignant peritoneal mesothelioma, pseudomyxoma peritonei, malignant ascites, sarcomatosis, and peritoneal carcinomatosis from gastrointestinal and ovarian cancers. Pharmacists may play a major role in optimizing intraperitoneal chemotherapy through verification of chemotherapy order for proper doses, dilution, preparation, and administration. Moreover, pharmacists are medication experts who can provide other health care professionals with the necessary drug information. Despite the local application of chemotherapy, intraperitoneal chemotherapy is not free of systemic side effects and can be associated with serious complications. The benefits of intraperitoneal chemotherapy should be weighed against its potential harm to maximize efficacy and to minimize morbidity and mortality as much as possible. The aim of this article is to review the current available literature regarding the safety and efficacy of intraperitoneal chemotherapy in cancer treatment.
Neuropsychiatric Symptoms and Regional Neocortical Atrophy in Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Rafii Michael S. , Taylor Curtis S. , Kim Hyun T. , Desikan Rahul S. , Fleisher Adam S. , Katibian David , Brewer James B. , Dale Anders M. , Aisen Paul S. 
Published: October 2013

Background: To assess the relationship between regional neocortical atrophy and psychotic symptoms in adults with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods: Rates of change in regional neocortical atrophy as measured by longitudinal magnetic resonance imaging scans and the occurrence of psychotic symptoms and/or the long-term use of antipsychotic medications in 389 outpatients with MCI or AD in Alzheimer’s Disease Neuroimaging Initiative. Results: Atrophy rate of 3 specific neocortical regions, lateral frontal, lateral parietal, and anterior cingulate gyrus, was significantly associated with the onset of psychosis including delusions, agitation, wandering, and hallucinations and/or the need for chronic antipsychotic medications. Atrophy rate of the lateral frontal lobe correlated most significantly with onset of psychotic symptoms or need for chronic antipsychotic medications. Conclusions: Psychosis was associated with volume loss in specific regions of the lateral frontal and parietal lobes as well as anterior cingulate gyrus.
Body composition and gene expression QTL mapping in mice reveals imprinting and interaction effects
Authors: Cheng Ye , Rachagani Satyanarayana , Cánovas Angela , Mayes Mary Sue , Tait Richard G , Dekkers Jack CM , Reecy James M 
Published: October 2013

Abstract

Background
Shifts in body composition, such as accumulation of body fat, can be a symptom of many chronic human diseases; hence, efforts have been made to investigate the genetic mechanisms that underlie body composition. For example, a few quantitative trait loci (QTL) have been discovered using genome-wide association studies, which will eventually lead to the discovery of causal mutations that are associated with tissue traits. Although some body composition QTL have been identified in mice, limited research has been focused on the imprinting and interaction effects that are involved in these traits. Previously, we found that Myostatin genotype, reciprocal cross, and sex interacted with numerous chromosomal regions to affect growth traits.

Results
Here, we report on the identification of muscle, adipose, and morphometric phenotypic QTL (pQTL), translation and transcription QTL (tQTL) and expression QTL (eQTL) by applying a QTL model with additive, dominance, imprinting, and interaction effects. Using an F2 population of 1000 mice derived from the Myostatin-null C57BL/6 and M16i mouse lines, six imprinted pQTL were discovered on chromosomes 6, 9, 10, 11, and 18. We also identified two IGF1 and two Atp2a2 eQTL, which could be important trans-regulatory elements. pQTL, tQTL and eQTL that interacted with Myostatin, reciprocal cross, and sex were detected as well. Combining with the additive and dominance effect, these variants accounted for a large amount of phenotypic variation in this study.

Conclusions
Our study indicates that both imprinting and interaction effects are important components of the genetic model of body composition traits. Furthermore, the integration of eQTL and traditional QTL mapping may help to explain more phenotypic variation than either alone, thereby uncovering more molecular details of how tissue traits are regulated.