bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reverse engineering of an aspirin-responsive regulator in bacteria
Authors: Oliveira Monteiro Lummy Maria , Arruda Letícia Magalhães , Medeiros Ananda Sanches , Martins-Santana Leonardo , Fátima Alves Luana de , Guazzaroni María-Eugenia , Lorenzo Víctor de , Silva-Rocha Rafael 
Published: August 2018

AbstractBacterial transcriptional factors (TFs) and their target promoters are key devices for engineering of complex circuits in many biotechnological applications. Yet, there is a dearth of well characterized inducer-responsive TFs that could be used in the context of an animal or human host. In this work we have deciphered the inducer recognition mechanism of two AraC/XylS regulators from Pseudomonas putida (BenR and XylS) for creating a novel expression system responsive to acetyl salicylate (i.e. Aspirin). Using protein homology modeling and molecular docking with the cognate inducer benzoate and a suite of chemical analogues, we identified the conserved binding pocket of these two proteins. Using site directed mutagenesis, we identified a single amino acid position required for efficient inducer recognition and transcriptional activation. While modification of this position in BenR abolishes protein activity, its modification in XylS increases the response to several aromatic compounds, including acetyl salicylic acid to levels close to those achieved by the canonical inducer. Moreover, by constructing chimeric proteins with swapped N-terminal domains, we created novel regulators with mixed promoter and inducer recognition profiles. As a result, a collection of engineered TFs was generated with enhanced response to a well characterized and largely innocuous molecule with a potential for eliciting heterologous expression of bacterial genes in animal carriers.
Bcl-xL inhibition enhances Dinaciclib-induced cell death in soft-tissue sarcomas
Authors: Rello-Varona Santi , Fuentes-Guirado Miriam , López-Alemany Roser , Contreras-Pérez Aida , Mulet-Margalef Núria , García-Monclús Silvia , Tirado Oscar M. , García del Muro Xavier 
Published: August 2018

AbstractSoft-tissue sarcomas (STS) are an uncommon and heterogeneous group of malignancies that result in high mortality. Metastatic STS have very bad prognosis due to the lack of effective treatments. Dinaciclib is a model drug for the family of CDK inhibitors. Its main targets are cell cycle regulator CDK1 and protein synthesis controller CDK9. We present data supporting Dinaciclib ability to inactivate in vitro different STS models at nanomolar concentrations. Moreover, the different rhythms of cell death induction allow us to further study into the mechanism of action of the drug. Cell death was found to respond to the mitochondrial pathway of apoptosis. Anti-apoptotic Bcl-xL was identified as the key regulator of this process. Bcl-xL showed a slower decay curve after protein synthesis disruption that in tolerant cell lines was enough to delay apoptosis, as its action cannot be countered by the relative low levels of pro-apoptotic BH3 proteins BIM and PUMA. Combination of Dinaciclib with BH3-mimetics led to quick and massive apoptosis induction in vitro, but in vivo assessment was prevented due to liver toxicity. Additionally, Bcl-xL inhibitor A-1331852 also synergized with conventional chemotherapy drugs as Gemcitabine. Thus, Bcl-xL targeted therapy arises as a major opportunity to the treatment of STS.
Inferring the molecular mechanisms of noncoding Alzheimer’s disease-associated genetic variants
Authors: Amlie-Wolf Alexandre , Tang Mitchell , Way Jessica , Dombroski Beth , Jiang Ming , Vrettos Nicholas , Chou Yi-Fan , Zhao Yi , Kuzma Amanda , Mlynarski Elisabeth E. , Leung Yuk Yee , Brown Christopher D. , Wang Li-San , Schellenberg Gerard D. 
Published: August 2018

Structured AbstractINTRODUCTIONWe set out to characterize the causal variants, regulatory mechanisms, tissue contexts, and target genes underlying noncoding late-onset Alzheimer’s Disease (LOAD)-associated genetic signals.METHODSWe applied our INFERNO method to the IGAP genome-wide association study (GWAS) data, annotating all potentially causal variants with tissue-specific regulatory activity. Bayesian co-localization analysis of GWAS summary statistics and eQTL data was performed to identify tissue-specific target genes.RESULTSINFERNO identified enhancer dysregulation in all 19 tag regions analyzed, significant enrichments of enhancer overlaps in the immune-related blood category, and co-localized eQTL signals overlapping enhancers from the matching tissue class in ten regions (ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, EPHA1, FERMT2, ZCWPW1). We validated the allele-specific effects of several variants on enhancer function using luciferase expression assays.DISCUSSIONIntegrating functional genomics with GWAS signals yielded insights into the regulatory mechanisms, tissue contexts, and genes affected by noncoding genetic variation associated with LOAD risk.
EVR: Reconstruction of Bacterial Chromosome 3D Structure Using Error-Vector Resultant Algorithm
Authors: Hua Kang-Jian , Ma Bin-Guang 
Published: August 2018

ABSTRACTMore and more 3C/Hi-C experiments on prokaryotes have been published. However, most of the published modeling tools for chromosome 3D structures are targeting at eukaryotes. How to transform prokaryotic experimental chromosome interaction data into spatial structures is an important task and in great need. We have developed a new reconstruction program for bacterial chromosome 3D structures called EVR that exploits a simple Error-Vector Resultant (EVR) algorithm. This software tool is particularly optimized for the closed-loop structural features of prokaryotic chromosomes. EVR can be used to reconstruct the bacterial 3D chromosome structure based on the contact frequency matrix derived from 3C/Hi-C experimental data quickly and precisely.
Escherichia coli ST131-
H
22 as a Foodborne Uropathogen
Authors: Liu Cindy M. , Stegger Marc , Aziz Maliha , Johnson Timothy J. , Waits Kara , Nordstrom Lora , Gauld Lori , Weaver Brett , Rolland Diana , Statham Sally , Horwinski Joseph , Sariya Sanjeev , Davis Gregg S. , Sokurenko Evgeni , Keim Paul , Johnson James R. , Price Lance B. 
Published: August 2018

E. coli
ST131 is an important extraintestinal pathogen that can colonize the gastrointestinal tracts of humans and food animals. Here, we combined detection of accessory traits associated with avian adaptation (ColV plasmids) with high-resolution phylogenetics to quantify the portion of human infections caused by ST131 strains of food animal origin. Our results suggest that one ST131 sublineage—ST131-
H
22—has become established in poultry populations around the world and that meat may serve as a vehicle for human exposure and infection. ST131-
H
22 is just one of many
E. coli
lineages that may be transmitted from food animals to humans. Additional studies that combine detection of host-associated accessory elements with phylogenetics may allow us to quantify the total fraction of human extraintestinal infections attributable to food animal
E. coli
strains.
NADPH Oxidase and Guanylate Binding Protein 5 Restrict Survival of Avirulent Type III Strains of Toxoplasma gondii in Naive Macrophages
Authors: Matta Sumit K. , Patten Kelley , Wang Quiling , Kim Bae-Hoon , MacMicking John D. , Sibley L. David 
Published: August 2018

Toxoplasmainfections in humans and other mammals are largely controlled by IFN-γ produced by the activated adaptive immune system. However, we still do not completely understand the role of cell-intrinsic functions in controllingToxoplasmaor other apicomplexan infections. The present work identifies intrinsic activities in naive macrophages in counteractingT. gondiiinfection. Using an avirulent strain ofT. gondii, we highlight the importance of Nox complexes in conferring protection against parasite infection bothin vitroandin vivo. We also identify Gbp5 as a novel macrophage factor involved in limiting intracellular infection by avirulent strains ofT. gondii. The rarity of human infections caused by type III strains suggests that these mechanisms may also be important in controlling human toxoplasmosis. These findings further extend our understanding of host responses and defense mechanisms that act to control parasitic infections at the cellular level.
Health-Related Quality of Life and Sexual Function in Patients Treated for Penile Cancer
Authors: Suarez-Ibarrola Rodrigo , Cortes-Telles Arturo , Miernik Arkadiusz 
Published: August 2018

<b><i>Purpose:</i></b> To assess the impact of primary surgery, partial and total penectomy, and of inguinal lymphadenectomy on health-related quality of life (HRQoL) and the sexual function of penile cancer patients. <b><i>Materials and Methods:</i></b> We invited 15 patients surgically treated for penile cancer in the Regional Hospital of Specialized Medicine of the Yucatan Peninsula between 2012 and 2016 to complete the SF-36 quality of life and International Index of Erectile Function (IIEF-5) sexual function questionnaires. We evaluated the impact of primary surgery type and inguinal lymphadenectomy on the outcome of HRQoL and sexual function. <b><i>Results:</i></b> A total of 10 patients (66%) completed the SF-36 questionnaire. Surgery type and extent of resection were overall not associated significantly with worse outcomes on the assessed domains of quality of life. However, men treated with partial penectomy reported significantly more pain (<i>p</i> = 0.0547) than men treated with total penectomy. Similarly, men who underwent lymphadenectomy reported significantly more pain (<i>p</i> = 0.0547) than those who were spared from the procedure due to the ­primary tumor´s stage and grade. Sexual function was severely affected (IIEF mean = 6.5) in patients treated with partial penectomy. <b><i>Conclusions:</i></b> Although partial penectomy and lymphadenectomy were significantly associated with more postoperative pain, no differences were observed in other HRQoL domains. Sexual function was severely affected in patients treated with partial penectomy.
A Neotropical armored harvestman (Arachnida, Opiliones) uses proprioception and vision for homing
Authors: Silva Norton Felipe dos Santos , Fowler-Finn Kasey , Ribeiro Mortara Sara , Hirata Willemart Rodrigo 
Published: August 2018

AbstractAnimals use external and/or internal cues to navigate and can show flexibility in cue use if one type of cue is unavailable. We studied the homing ability of the harvestmanHeteromitobates discolor(Arachnida, Opiliones) by moving egg-guarding females from their clutches. We tested the importance of vision, proprioception, and olfaction. We predicted that homing would be negatively affected in the absence of these cues, with success being measured by the return of females to their clutches. We restricted proprioception by not allowing females to walk, removed vision by painting the eyes, and removed the odours by removing the clutch and cleaning its surroundings. We found that vision is important for homing, and in the absence of visual cues, proprioception is important. Finally, we found increased homing when eggs were present, and that the time of the day also influenced homing. We highlight vision as a previously overlooked sensory modality in Opiliones.
A New Interpretation of the Final Days of the Jewish Community of Pamiers
Authors: Ben-Shalom Ram 
Published: August 2018

Abstract
This article examines, and publishes in an annex, a letter written by Yom Tov ben Hannah of Montalbán. This letter describes how the seventy Jews of Pamiers were forced to raise money to ransom their lives. Henri Gross presumed that it was count Gaston III of Foix (d. 1391), who had tried to extort money from the Jewish community. A re-examination suggests that the imprisonment of the Jews of Pamiers occurred after the promulgation of the edict of expulsion from France (1394), and represented a final attempt by count Mathieu of Foix, to extort money before the Jews’ departure.
Applying Additional Protocol II of the Geneva Conventions to the United Nations Forces
Authors: Sergeev Artem 
Published: August 2018

Following the widespread participation of United Nations (UN) forces in hostile environments, this article aims to expand the obligations of the UN under International Humanitarian Law. The article argues that Additional Protocol II (AP II) to the Geneva Conventions can bind UN forces, even though the UN is not formally a party thereto. The argument is built on three distinct legal issues: the first issue is whether the UN’s involvement in a conflict internationalizes a non-international armed conflict; the second issue is the legal nature of the UN’s obligations under AP II, which will be explained through two legal theories of indirect consent; and the third issue is the conformity of UN forces to the criteria of an armed group outlined in AP II. The article concludes that if UN forces meet certain conditions, as will be outlined herein, they should be bound by the provisions contained in AP II.
Relative Dispersion of Surface Drifters in the Benguela Upwelling Region
Authors: Dräger-Dietel J. , Jochumsen K. , Griesel A. , Badin G. 
Published: August 2018

AbstractWe examine the relative dispersion of surface drifters deployed in groups of triplets at the boundaries of a filament in the upwelling region off Namibia for both the entire ensemble and the two main subgroups. For the drifters in the group released at the northern boundary of the filament, close to the upwelling front, we find that the mean-square pair separation 〈s2(t)〉 shows the characteristic distinct dispersion regimes [nonlocal, local (Richardson), and diffusive] of an ocean surface mixed layer. We confirm the different dispersion regimes by a rescaled presentation of the moments 〈sn(t)〉 and thereby also explain the anomalous slow decay of the kurtosis in the transient regime. For the drifter group released at the southern boundary, 〈s2(t)〉 remains constant for a short period, followed by a steep “Richardson like” increase and an asymptotic diffusive increase. In contrast to the northern release, the corresponding moments reveal a narrow distribution of pair separations for all regimes. The analysis of finite-size Lyapunov exponents (FSLEs) reveals consistent results when applied to the two releases separately. When applied to the entire drifter ensemble, the two measures yield inconsistent results. We relate the breakdown of consistency to the impact of the different dynamics on the respective averages: whereas, because of separation in scale, 〈s2(t)〉 is dominated by the northern release, the decay of the FSLEs for small distances reflects the drifter dynamics within the filament.
Assimilation of Argo Temperature and Salinity Profiles Using a Bias-Aware EnOI Scheme for the Labrador Sea
Authors: Scott K. Andrea , Chen Changheng , Myers Paul G. 
Published: August 2018

AbstractIn this study, temperature and salinity profiles from Argo floats are assimilated into a coupled ice–ocean model over the North Atlantic Ocean and Arctic using an ensemble optimal interpolation (EnOI) scheme, with the aim of improving the thermohaline structure of the Labrador Sea estimated by the model. Data assimilation experiments are carried out from September 2014 to April 2015 both with and without a one-step bias correction method from the literature. It is found that assimilation of the Argo profiles reduces the errors in the model temperature and salinity when verification is done against both withheld Argo profiles and sea surface temperature from satellite data. The assimilation also leads to deeper mixed layer depth in the Labrador Sea, closer to observations shown in other studies, in particular when bias correction is used. We hypothesize that this is because the bias field leads to vertical density profiles that are less stratified, and hence requiring less energy for mixing, than when bias correction is not used.
The impact of fibromyalgia syndrome and the role of comorbidity with mood and post-traumatic stress disorder in worsening the quality of life
Authors: Carta Mauro Giovanni , Moro Maria Francesca , Pinna Francesca Laura , Testa Giorgia , Cacace Enrico , Ruggiero Valeria , Piras Martina , Romano Ferdinando , Minerba Luigi , Machado Sergio , Freire Rafael Christophe , Nardi Antonio Egidio , Sancassiani Federica 
Published: August 2018

Background: The aim is to measure the association between fibromyalgia syndrome (FMS) and post-traumatic stress disorder (PTSD), mood and anxiety disorders using reliable psychiatric diagnoses according to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) and with a case–control design. Methods: Case–control study with cases (71 consecutive female patients with FMS) and controls (284 subjects without FMS), randomly drawn after a gender- and age-matching technique from the database of an epidemiological survey. Psychiatric diagnoses were conducted according to DSM-IV and carried out by clinical staff using a structured interview (Advanced Neuropsychiatric Tools and Assessment Schedule). QoL was measured by Short Form Health Survey (SF-12). Results: The lifetime prevalence of major depressive disorder (MDD; 43.7% vs 8.1%, p < .0001), bipolar disorder (BD; 21.1% vs 0.7%, p  < .0001), PTSD (8.4% vs 1.4%, p < .0001) and panic disorder (28.2% vs 5.6%, p < .001) was higher in people with FMS than in controls. People with FMS showed a poorer QoL than controls on the SF-12 (26.43 ± 6.04 vs 37.45 ± 5.80, p < .0001). Those with comorbidity with MDD and BD showed a mean SF-12 score of 24.75 ± 6.31 versus 29.52 ± 4.84 ( N = 25) of people with FMS without any mood disorder ( p = .002). The attributable burden of FMS in worsening QoL was found comparable to that of serious chronic diseases such as multiple sclerosis. Conclusion: FMS is a disorder that ‘in itself’ can have a devastating impact on an individual’s life. The frequency of the association with major depressive and bipolar disorders increases the impact on the QoL of people with FMS. One of the causes of this association appears to be the extreme vulnerability to chronic stress that this disorder involves. The findings have important clinical significance: the physician must interpret in the right dimension and with dignity the suffering of the people with FMS.
Endonasal Sinus Surgery: Extended versus Limited Approach
Authors: Kuehnemund Matthias , Lopatin Andrej , Amedee Ronald G. , Mann Wolf J. 
Published: August 2018

Background This study was designed to investigate whether two different surgical approaches in endonasal sinus surgery lead to different postoperative results in patients with chronic rhinosinusitis. Methods Sixty-five patients suffering from chronic rhinosinusitis were operated on with either a limited approach or an extended approach. They were examined preoperatively and reassessed during 3 months, 6 months, and long-term follow-up visits that included endoscopy, saccharin transport time, and the assessment of symptoms. Results The concept of this study was prospective, randomized, and multicenter (Mainz, Germany, and Moscow, Russia). The results of the two different surgical approaches were compared with each other. Conclusion Surgical results and symptomatology were similar in both groups of patients, suggesting that a conservative approach may be sufficient in most patients.
Management of Severe Bilateral Nasal Wall Collapse
Authors: Stucker Fred J. , Lian Timothy , Sanders Kenneth 
Published: August 2018

Objective The aim of this study was to examine and analyze the pathology contributing to severe bilateral nasal wall collapse seen in certain revision rhinoplasty patients and identify those surgical maneuvers in the previous nasal surgery, which may have contributed to this complication; suggest alternatives or modifying steps in nasal surgery to prevent lateral wall collapse; analyze consecutive revision rhinoplasties and identify those patients who have complete bilateral nasal collapse at the internal nasal valve; and analyze the results achieved after surgical reconstruction of complete bilateral nasal collapse. Patients We identified 49 patients, who presented from 1990 to 2000 for revision surgery, who had bilateral collapse of the upper lateral cartilage. All patients had at least one previous rhinoplasty and all but 14 patients had undergone two or more procedures. The patients were reconstructed with a conchal cartilage graft placed through an external rhinoplasty approach. Results All patients complained of nasal obstruction with forced nasal inspiration. The collapse was visualized on inspiration and when prevented with intranasal positioning of a bayonet, all patients experienced an immediate improvement in nasal breathing. Postoperatively, all patients experienced this same improvement in their nasal airway. Collapse was not identified in any of the patients after surgery. Two patients underwent revision because of cosmetic asymmetries. Conclusion We strongly recommend a cartilage overlay to reconstitute the rigid midline continuity of the upper lateral cartilages. Unfortunately, with any significant hump removal, this structural interruption is, to varying degrees, inevitable in most rhinoplasty techniques. The upper lateral cartilages can be sutured to circumvent some of the inferior drift, but this will not reconstitute the rigid lateral cantilever effect of the intact cartilage.
Resection of the Inferior Superior Turbinate: Does it Affect Olfactory Ability or Contain Olfactory Neuronal Tissue?
Authors: Say Phillip , Leopold Donald , Cochran Gregory , Smith Lynette , Greiner Tim 
Published: August 2018

Background One approach to the sphenoid sinus involves resection of the inferior portion of the superior turbinate. There is general agreement from anatomic investigations that this area contains olfactory mucosa. This study will determine if olfactory tissue can be found in the superior turbinate mucosa of patients with chronic sphenoiditis and what effect its removal has on a patient's olfactory ability. Methods The inferior one-third of the superior turbinate removed during endoscopic sphenoidotomy was stained with olfactory marker protein antibody, a marker for mature olfactory tissue. The specimens were graded for content of olfactory neuronal elements. All patients underwent uninasal 12-item smell identification testing before surgery and at least 3 weeks after surgery. Results Fifty-five superior turbinate samples were taken from 31 patients. Nine (16%) of 55 samples contained olfactory neuronal elements that stained with olfactory marker protein. When comparing the pre- and postoperative smell test results, 52% of the nostrils had no more than a one-item change, 35% of the nostrils had a more than one-item improvement, and only 12% had more than a one-item loss. None of the nostrils with a loss of olfactory ability after the surgery showed olfactory neuronal elements in their superior turbinate specimens. Conclusion There is olfactory mucosa in approximately one-sixth of the superior turbinate specimens removed during the endoscopic transethmoidal sphenoidotomy procedure. Although 12% of the patients had a loss of olfactory ability in this study, none of the loss could be attributed to excision of olfactory tissue.