bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular basis of influenza hemagglutinin inhibition with an entry-blocker peptide by computational docking and mass spectrometry
Authors: Lu Robert , Müller Patrick , Downard Kevin M 
Published: January 2016

Background The increased resistance of circulating strains to current antiviral inhibitors of the influenza virus necessitates that new antivirals and their mode of action are identified. Influenza hemagglutinin is an ideal target given inhibitors of its function can block the entry of the virus into host cells during the early stages of replication. This article describes the molecular basis for the inhibition of H1 and H5 hemagglutinin by an entry-blocker peptide using companion molecular docking and mass spectrometry-based experiments. Methods A combination of hemagglutination inhibition assays, computational molecular docking and a novel mass spectrometry-based approach are employed to explore the mode of action of the entry-blocker peptide at a molecular level. Results The entry-blocker peptide is shown to be able to maximally inhibit blood cell hemagglutination at a concentration of between 6.4 and 9.2 µM. The molecular basis for this inhibition is derived from the binding of the peptide to hemagglutinin in the vicinity of the reported sialic acid binding site surrounded by an α-helix (190-helix) and two loop (130-loop and 220-loop) regions in the case of a H1 hemagglutinin and the second loop region in the case of a H5 hemagglutinin. Conclusions The results support the recognized potential of the entry-blocker peptide as an effective antiviral agent that can inhibit the early stages of viral replication and further illustrate the power of a combination of docking and a mass spectrometry approach to screen the molecular basis of new antiviral inhibitors to the influenza virus.
Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology
Authors: Zhang Dachuan , Xu Chunliang , Manwani Deepa , Frenette Paul S. 
Published: January 2016

Abstract
Sickle cell disease (SCD) is a severe genetic blood disorder characterized by hemolytic anemia, episodic vaso-occlusion, and progressive organ damage. Current management of the disease remains symptomatic or preventative. Specific treatment targeting major complications such as vaso-occlusion is still lacking. Recent studies have identified various cellular and molecular factors that contribute to the pathophysiology of SCD. Here, we review the role of these elements and discuss the opportunities for therapeutic intervention.
Beyond hydroxyurea: new and old drugs in the pipeline for sickle cell disease
Authors: Telen Marilyn J. 
Published: January 2016

Abstract
Despite Food and Drug Administration (FDA) approval of hydroxyurea to reduce the frequency of vaso-occlusive episodes, sickle cell disease (SCD) has continued to be treated primarily with analgesics for pain relief. However, elucidation of the multiple pathophysiologic mechanisms leading to vaso-occlusion and tissue injury in SCD has now resulted in a burgeoning effort to identify new treatment modalities to prevent or ameliorate the consequences of the disease. Development of new drugs as well as investigation of drugs previously used in other settings have targeted cell adhesion, inflammatory pathways, upregulation of hemoglobin F, hemoglobin polymerization and sickling, coagulation, and platelet activation. Although these efforts have not yet yielded drugs ready for FDA approval, several early studies have been extremely encouraging. Moreover, the marked increase in clinical pharmaceutical research addressing SCD and the new and old drugs in the pipeline make it reasonable to expect that we will soon have new treatments for SCD.
Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease
Authors: Hoban Megan D. , Orkin Stuart H. , Bauer Daniel E. 
Published: January 2016

AbstractEffective medical management for sickle cell disease (SCD) remains elusive. As a prevalent and severe monogenic disorder, SCD has been long considered a logical candidate for gene therapy. Significant progress has been made in moving toward this goal. These efforts have provided substantial insight into the natural regulation of the globin genes and illuminated challenges for genetic manipulation of the hematopoietic system. The initial γ-retroviral vectors, next-generation lentiviral vectors, and novel genome engineering and gene regulation approaches each share the goal of preventing erythrocyte sickling. After years of preclinical studies, several clinical trials for SCD gene therapies are now open. This review focuses on progress made toward achieving gene therapy, the current state of the field, consideration of factors that may determine clinical success, and prospects for future development.
Aligning the unalignable: bacteriophage whole genome alignments
Authors: Bérard Sèverine , Chateau Annie , Pompidor Nicolas , Guertin Paul , Bergeron Anne , Swenson Krister M. 
Published: January 2016

Abstract
Background
In recent years, many studies focused on the description and comparison of large sets of related bacteriophage genomes. Due to the peculiar mosaic structure of these genomes, few informative approaches for comparing whole genomes exist: dot plots diagrams give a mostly qualitative assessment of the similarity/dissimilarity between two or more genomes, and clustering techniques are used to classify genomes. Multiple alignments are conspicuously absent from this scene. Indeed, whole genome aligners interpret lack of similarity between sequences as an indication of rearrangements, insertions, or losses. This behavior makes them ill-prepared to align bacteriophage genomes, where even closely related strains can accomplish the same biological function with highly dissimilar sequences.

Results
In this paper, we propose a multiple alignment strategy that exploits functional collinearity shared by related strains of bacteriophages, and uses partial orders to capture mosaicism of sets of genomes. As classical alignments do, the computed alignments can be used to predict that genes have the same biological function, even in the absence of detectable similarity. The Alpha aligner implements these ideas in visual interactive displays, and is used to compute several examples of alignments of Staphylococcus aureus and Mycobacterium bacteriophages, involving up to 29 genomes. Using these datasets, we prove that Alpha alignments are at least as good as those computed by standard aligners. Comparison with the progressiveMauve aligner – which implements a partial order strategy, but whose alignments are linearized – shows a greatly improved interactive graphic display, while avoiding misalignments.

Conclusions
Multiple alignments of whole bacteriophage genomes work, and will become an important conceptual and visual tool in comparative genomics of sets of related strains.
A python implementation of Alpha, along with installation instructions for Ubuntu and OSX, is available on bitbucket (https://bitbucket.org/thekswenson/alpha).
PTESFinder: a computational method to identify post-transcriptional exon shuffling (PTES) events
Authors: Izuogu Osagie G. , Alhasan Abd A. , Alafghani Hani M. , Santibanez-Koref Mauro , Elliott David J. , Jackson Michael S. 
Published: January 2016

Abstract
Background
Transcripts, which have been subject to Post-transcriptional exon shuffling (PTES), have an exon order inconsistent with the underlying genomic sequence. These have been identified in a wide variety of tissues and cell types from many eukaryotes, and are now known to be mostly circular, cytoplasmic, and non-coding. Although there is no uniformly ascribed function, several have been shown to be involved in gene regulation. Accurate identification of these transcripts can, however, be difficult due to artefacts from a wide variety of sources.

Results
Here, we present a computational method, PTESFinder, to identify these transcripts from high throughput RNAseq data. Uniquely, it systematically excludes potential artefacts emanating from pseudogenes, segmental duplications, and template switching, and outputs both PTES and canonical exon junction counts to facilitate comparative analyses. In comparison with four existing methods, PTESFinder achieves highest specificity and comparable sensitivity at a variety of read depths. PTESFinder also identifies between 13 % and 41.6 % more structures, compared to publicly available methods recently used to identify human circular RNAs.

Conclusions
With high sensitivity and specificity, user-adjustable filters that target known sources of false positives, and tailored output to facilitate comparison of transcript levels, PTESFinder will facilitate the discovery and analysis of these poorly understood transcripts.
The Banach contraction principle in $C^{*}$-algebra-valued b-metric spaces with application
Authors: Kamran Tayyab , Postolache Mihai , Ghiura Adrian , Batul Samina , Ali Rashid 
Published: January 2016

AbstractWe introduce the notion of a $C^{*}$

C
∗

-algebra-valued b-metric space. We generalize the Banach contraction principle in this new setting. As an application of our result, we establish an existence result for an integral equation in a $C^{*}$

C
∗

-algebra-valued b-metric space.
Pedal Edema and Jugular Venous Pressure for Volume Overload in Peritoneal Dialysis Patients
Authors: Garfinkle Michael A. , Barton James 
Published: January 2016

Background: The diagnostic strength of the jugular venous pressure (JVP) and pedal edema as physical examination tools for the assessment of volume status has been minimally studied. Methods: We conducted a prospective observational study in an outpatient peritoneal dialysis clinic in Saskatoon, Canada. Patients were adult (age 18 or older) peritoneal dialysis outpatients without any history of cardiac dysfunction, a central line, and current arteriovenous fistula. JVP was assessed by both a resident and a staff nephrologist, while the presence of edema was assessed by the resident only. Likelihood ratios were calculated for the absence or presence of pedal edema as well as the JVP at multiple cutoffs. The criterion standard for volume overload was defined as an overhydration to extracellular water ratio of greater than or equal to 7 % as determined by bioimpedance (Body Composition Monitor—Fresnius Medical Care). Results: Twenty-five separate patient encounters were assessed. Twelve patients were found to be volume overloaded while 13 were euvolemic. The presence and absence of edema were both significant signs for the presence (+likelihood ratio (LR) 16, 95 % confidence interval (CI) 1.02–260) or absence (−LR 0.44, 95 % CI 0.23–0.83) of volume overload, respectively. The JVP failed to reach statistical significance for the presence or absence of volume overload at any height above the sternal angle, although precision was poor for the positive likelihood ratio at cutoffs above 3 cm and the negative likelihood ratio at the 0 cm cutoff. Conclusions: The presence of pedal edema is a good indicator of volume overload in peritoneal dialysis patients without cardiac dysfunction, although its absence cannot definitively rule out significant water excess. A JVP of 1 to 3 cm was found to be not a clinically significant sign. We are unable to comment on the diagnostic strength of a low (0 cm) or high (JVP >3 cm) due to poor precision.
Reduction of Inappropriate Prophylactic Pegylated Granulocyte Colony-Stimulating Factor Use for Patients With Non–Small-Cell Lung Cancer Who Receive Chemotherapy: An ASCO Quality Training Program Project of the Cleveland Clinic Taussig Cancer Institute
Authors: Martin Goodman Lindsey , Moeller Machelle B. , Azzouqa Abdel-Ghani , Guthrie Amy E. , Dalby Carole K. , Earl Marc A. , Cheng Connie , Pennell Nathan A. , Shapiro Marc , Velcheti Vamsidhar , Stevenson James P. 
Published: January 2016

Purpose: Routine prophylactic pegylated granulocyte colony-stimulating factor (pGCSF) administration for patients receiving chemotherapy regimens associated with low risk (< 10%) for neutropenic fever (LRNF) is not recommended. Inappropriate use of pGCSF increases patient morbidity and health care costs. Methods: A multidisciplinary team reviewed the charts of patients with non–small-cell lung cancer (NSCLC) at the Taussig Cancer Institute in whom a new chemotherapy regimen was initiated from April through November 2013. pGCSF use was identified and deemed appropriate if prescribed for chemotherapy associated with high risk of neutropenic fever (> 20%) or intermediate risk (10% to 20%) if other risk factors for neutropenic fever were present. Use with LRNF chemotherapy was recorded as inappropriate. Results: One hundred eighty patients with NSCLC received a new chemotherapy regimen during the specified time period. Thirty-four of 119 patients (28%) treated with LRNF chemotherapy received pGCSF. Each patient received an average of 2.6 doses of pGCSF (total, 89 doses). We implemented three plan-do-study-act cycles: education of providers, development of Taussig Cancer Institute consensus guidelines for pGCSF in NSCLC, and removal of standing pGCSF orders from LRNF chemotherapy in the electronic medical record. Analysis during the change period revealed 4% of patients with NSCLC treated with LRNF chemotherapy received pGCSF. Cost analysis showed an 84% decrease in billed charges per month. No increase in neutropenic fever admissions was found. Conclusion: pGCSF was excessively prescribed for patients with NSCLC. Factors contributing to inappropriate use included provider lack of familiarity with guidelines and knowledge with regard to the risk of neutropenic fever for individual chemotherapy regimens, and electronic medical record chemotherapy templates that contain standing GCSF orders. Interventions to address these gaps quickly produced improved compliance with guidelines and led to significant cost savings.
Weight Loss Is Associated With Increased NAD+/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue
Authors: Rappou Elisabeth , Jukarainen Sakari , Rinnankoski-Tuikka Rita , Kaye Sanna , Heinonen Sini , Hakkarainen Antti , Lundbom Jesper , Lundbom Nina , Saunavaara Virva , Rissanen Aila , Virtanen Kirsi A. , Pirinen Eija , Pietiläinen Kirsi H. 
Published: January 2016

Abstract

Context:
Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs) are 2 important nicotinamide adenine dinucleotide (NAD)+-dependent enzyme families with opposing metabolic effects. Energy shortage increases NAD+ biosynthesis and SIRT activity but reduces PARP activity in animals. Effects of energy balance on these pathways in humans are unknown.

Objective:
We compared NAD+/SIRT pathway expressions and PARP activities in sc adipose tissue (SAT) between lean and obese subjects and investigated their change in the obese subjects during a 12-month weight loss.

Design, Setting and Participants:
SAT biopsies were obtained from 19 clinically healthy obese subjects (mean ± SE body mass index, 34.6 ± 2.7 kg/m2) during a weight-loss intervention (0, 5, and 12 mo) and from 19 lean reference subjects (body mass index, 22.7 ± 1.1 kg/m2) at baseline.

Main Outcome Measures:
SAT mRNA expressions of SIRTs 1–7 and the rate-limiting gene in NAD+ biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT) were measured by Affymetrix, and total PARP activity by ELISA kit.

Results:
SIRT1, SIRT3, SIRT7, and NAMPT expressions were significantly lower, whereas total PARP activity was increased in obese compared with lean subjects. SIRT1 and NAMPT expressions increased in obese subjects between 0 and 5 months, after a mean weight loss of 11.7%. In subjects who continued to lose weight between 5 and 12 months, SIRT1 expression increased progressively, whereas in subjects with weight regain, SIRT1 reverted to baseline levels. PARP activity significantly decreased in all subjects upon weight loss.

Conclusions:
Calorie restriction is an attractive strategy to improve the NAD+/SIRT pathway and decrease PARPs in SAT in human obesity.
KIF17 regulates RhoA-dependent actin remodeling at epithelial cell–cell adhesions
Authors: Acharya Bipul R. , Espenel Cedric , Libanje Fotine , Raingeaud Joel , Morgan Jessica , Jaulin Fanny , Kreitzer Geri 
Published: January 2016

ABSTRACT
The kinesin KIF17 localizes at microtubule plus-ends where it contributes to regulation of microtubule stabilization and epithelial polarization. We now show that KIF17 localizes at cell–cell adhesions and that KIF17 depletion inhibits accumulation of actin at the apical pole of cells grown in 3D organotypic cultures and alters the distribution of actin and E-cadherin in cells cultured in 2D on solid supports. Overexpression of full-length KIF17 constructs or truncation mutants containing the N-terminal motor domain resulted in accumulation of newly incorporated GFP–actin into junctional actin foci, cleared E-cadherin from cytoplasmic vesicles and stabilized cell–cell adhesions to challenge with calcium depletion. Expression of these KIF17 constructs also increased cellular levels of active RhoA, whereas active RhoA was diminished in KIF17-depleted cells. Inhibition of RhoA or its effector ROCK, or expression of LIMK1 kinase-dead or activated cofilinS3A inhibited KIF17-induced junctional actin accumulation. Interestingly, KIF17 activity toward actin depends on the motor domain but is independent of microtubule binding. Together, these data show that KIF17 can modify RhoA–GTPase signaling to influence junctional actin and the stability of the apical junctional complex of epithelial cells.
Removal of Phosphate from Aqueous Solution Using Layered Double Hydroxide Prepared from Waste Iron-Making Slag
Authors: Kuwahara Yasutaka , Tamagawa Shigetaka , Fujitani Tadahiro , Yamashita Hiromi 
Published: January 2016

Abstract
A layered double hydroxide (LDH) type adsorbent for phosphate removal from aqueous solution was prepared from blast furnace slag (BFS) which is vastly discharged by the iron manufacturing industry. The phosphate adsorption performances of the prepared adsorbent and its calcined derivatives were examined using simulated wastewater solutions containing 124 P-mg L−1 which is close to the effluent produced by the sewage sludge dewatering process, and factors such as pH, nature, and amount of adsorbent were studied to establish the optimum adsorption conditions. The adsorbent exhibited a great ability to efficiently remove phosphate in a variety of environments, especially even from 15 ppm phosphorus aqueous solutions, owing to a strong affinity of Ca(OH)x species and an ion-exchange ability of Cl− anions accommodated in the layers. The maximum phosphorus adsorption uptake reached 91.9 P-mg g−1 after 24 h of adsorption at an initial pH of 7.0 and at 25 °C, which was 126-fold higher than that of raw BFS (0.73 P-mg g−1). The adsorption process followed a pseudo-second-order kinetic model and Freundlich adsorption isotherms. The results suggest that the slag-made LDH is a promising low-cost adsorbent for efficient phosphate removal from wastewater streams and phosphorus recovery processes.
Flight and Digging Effort in Leaf-cutting Ant Males and Gynes
Authors: Silva Edypo Jacob , Camargo Roberto Da Silva , Forti Luiz Carlos 
Published: January 2016

The nuptial flight and nest digging are high intensity activities which consume body reserves. The flight and digging effort was quantified by measuring the carbohydrate and total lipids content in males and females before and after the nuptial flight, and the queen’s digging effort during the foundation. The digging effort was quantified by experimentally stimulating the queens to dig a nest – one, two or three consecutive times – compared to the queens that did not dig. The colorimetric method was used to determine the soluble carbohydrates and extraction method of immersion was used to determine the total lipids. The results showed significant loss of carbohydrates and total lipids in males and females after the flight. On average the males contained 0.027 mg of soluble carbohydrates before the nuptial flight, and 0.005 mg after the nuptial flight, and the females contained 0.129 mg of soluble carbohydrates before the nuptial flight, and 0.079 mg after the nuptial flight. For the males the percentage of lipids decreased from 5.27±1.07% to 2.60±0.63% and for females from 36.46±4.86% to 32.62% after the nuptial flight. The digging effort of the queen caused a slight reduction in total carbohydrates, it was without digging 0.054 mg, normal digging 0.055 mg, double digging 0.045 mg (decrease of 20,22 %), and triple digging 0.044 mg (decrease of 20 %) per queen. Based on our results we conclude that the carbohydrate content is the main energetic resource used for the nuptial flight and nest digging, for males and gynes of leaf-cutting ants.
Bioactivity of Cicuta virosa L. var. latisecta Celak. (Umbelliferae: Cicutal) against Red Imported Fire Ant under Laboratory and Field Conditions
Authors: Tian Yong-Qing , Cheng Dong-Mei , Zhang Zhi-Xiang 
Published: January 2016

We evaluated the bioactivities of compounds from Cicuta virosa L. var. latisecta Celak. against red imported fire ants (Solenopsis invicta Buren) under field and laboratory conditions. The compounds were as follows: methanol extract; petroleum ether, chloroform, and ethyl acetate fractions from the methanol extract; and the active compound isoimperatorin, which was isolated from the chloroform-fraction. The 7 d LC50 values of the methanol extract, petroleum ether, chloroform, and ethyl acetate fractions and isoimperatorin toward micrergates were 111.20, 214.45, 40.90, 569.67, and 25.73 mg/kg, res­pectively. The corresponding LC50 values toward macrergates were 155.78, 308.38, 75.01, 776.75, and 42.77 mg/kg, res­pectively. Under field conditions, baits containing 0.2% methanol extract, 0.1% chloroform fraction, and 0.05% isoimperatorin efficiently controlled S. invicta, with effectiveness percentages of 95.56%, 97.78%, and 95.56%, respectively on the 30th day after bait application. Such effectiveness percentages were not significantly different from that obtained using the positive control fipronil. The present study showed that C. virosa L. var. latisecta has potential as a natural control agent for the red imported fire ants.
Global elevational, latitudinal, and climatic limits for termites and the redescription of Rugitermes laticollis Snyder (Isoptera: Kalotermitidae) from the Andean Highlands
Authors: Scheffrahn Rudolf H 
Published: January 2016

We compile, map, and discuss global elevational, latitudinal, thermal, and rainfall extremes of termite localities from literature sources and unpublished records. Rugitermes laticollis from Ecuador and Bolivia occurs at higher elevation (2700-3600 m) than any other termite species. Termites span the globe from 54.3°N (Zootermopsis angusticollis in British Columbia (B.C.), Canada) to 48.9°S (Porotermes quadricollis in Magdalena, Chile). The coldest locality supporting termites (Reticulitermes sp.) is at Churn Creek, B.C., where the mean annual temperature is 4°C. Lake Havasu City, Arizona, where Heterotermes aureus and Gnathamitermes perplexus occur, has the highest recorded temperature maximum (52°C) for a termite locality. Cryptotermes brevis and Neotermes chilensis are endemic to the Pacific Coast of Peru and Chile where rain is essentially absent. We further provide locality extremes for six termite families from six zoogeographical regions. In addition, the winged imago of Ru. laticollis is redescribed and the soldier is described for the first time.