bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary Metabolism and Interspecific Competition Affect Accumulation of Spontaneous Mutants in the GacS-GacA Regulatory System in
Pseudomonas protegens
Authors: Yan Qing , Lopes Lucas D. , Shaffer Brenda T. , Kidarsa Teresa A. , Vining Oliver , Philmus Benjamin , Song Chunxu , Stockwell Virginia O. , Raaijmakers Jos M. , McPhail Kerry L. , Andreote Fernando D. , Chang Jeff H. , Loper Joyce E. 
Published: January 2018

ABSTRACT

Secondary metabolites are synthesized by many microorganisms and provide a fitness benefit in the presence of competitors and predators. Secondary metabolism also can be costly, as it shunts energy and intermediates from primary metabolism. In
Pseudomonas
spp., secondary metabolism is controlled by the GacS-GacA global regulatory system. Intriguingly, spontaneous mutations in
gacS
or
gacA
(Gac
−
mutants) are commonly observed in laboratory cultures. Here we investigated the role of secondary metabolism in the accumulation of Gac
−
mutants in
Pseudomonas protegens
strain Pf-5. Our results showed that secondary metabolism, specifically biosynthesis of the antimicrobial compound pyoluteorin, contributes significantly to the accumulation of Gac
−
mutants. Pyoluteorin biosynthesis, which poses a metabolic burden on the producer cells, but not pyoluteorin itself, leads to the accumulation of the spontaneous mutants. Interspecific competition also influenced the accumulation of the Gac
−
mutants: a reduced proportion of Gac
−
mutants accumulated when
P. protegens
Pf-5 was cocultured with
Bacillus subtilis
than in pure cultures of strain Pf-5. Overall, our study associated a fitness trade-off with secondary metabolism, with metabolic costs versus competitive benefits of production influencing the evolution of
P. protegens
, assessed by the accumulation of Gac
−
mutants.

IMPORTANCE
Many microorganisms produce antibiotics, which contribute to ecologic fitness in natural environments where microbes constantly compete for resources with other organisms. However, biosynthesis of antibiotics is costly due to the metabolic burdens of the antibiotic-producing microorganism. Our results provide an example of the fitness trade-off associated with antibiotic production. Under noncompetitive conditions, antibiotic biosynthesis led to accumulation of spontaneous mutants lacking a master regulator of antibiotic production. However, relatively few of these spontaneous mutants accumulated when a competitor was present. Results from this work provide information on the evolution of antibiotic biosynthesis and provide a framework for their discovery and regulation.
Simultaneous Binding of Multiple EF-Tu Copies to Translating Ribosomes in Live
Escherichia coli
Authors: Mustafi Mainak , Weisshaar James C. 
Published: January 2018

ABSTRACT

In bacteria, elongation factor Tu is a translational cofactor that forms ternary complexes with aminoacyl-tRNA (aa-tRNA) and GTP. Binding of a ternary complex to one of four flexible L7/L12 units on the ribosome tethers a charged tRNA in close proximity to the ribosomal A site. Two sequential tests for a match between the aa-tRNA anticodon and the current mRNA codon then follow. Because one elongation cycle can occur in as little as 50 ms and the vast majority of aa-tRNA copies are not cognate with the current mRNA codon, this testing must occur rapidly. We present a single-molecule localization and tracking study of fluorescently labeled EF-Tu in live
Escherichia coli
. Imaging at 2 ms/frame distinguishes 60% slowly diffusing EF-Tu copies (assigned as transiently bound to translating ribosome) from 40% rapidly diffusing copies (assigned as a mixture of free ternary complexes and free EF-Tu). Combining these percentages with copy number estimates, we infer that the four L7/L12 sites are essentially saturated with ternary complexes in vivo. The results corroborate an earlier inference that all four sites can simultaneously tether ternary complexes near the A site, creating a high local concentration that may greatly enhance the rate of testing of aa-tRNAs. Our data and a combinatorial argument both suggest that the initial recognition test for a codon-anticodon match occurs in less than 1 to 2 ms per aa-tRNA copy. The results refute a recent study (A. Plochowietz, I. Farrell, Z. Smilansky, B. S. Cooperman, and A. N. Kapanidis, Nucleic Acids Res 45:926–937, 2016,
https://doi.org/10.1093/nar/gkw787
) of tRNA diffusion in
E. coli
that inferred that aa-tRNAs arrive at the ribosomal A site as bare monomers, not as ternary complexes.

IMPORTANCE
Ribosomes catalyze translation of the mRNA codon sequence into the corresponding sequence of amino acids within the nascent polypeptide chain. Polypeptide elongation can be as fast as 50 ms per added amino acid. Each amino acid arrives at the ribosome as a ternary complex comprising an aminoacyl-tRNA (aa-tRNA), an elongation factor called EF-Tu, and GTP. There are 43 different aa-tRNAs in use, only one of which typically matches the current mRNA codon. Thus, ternary complexes must be tested very rapidly. Here we use fluorescence-based single-molecule methods that locate and track single EF-Tu copies in
E. coli
. Fast and slow diffusive behavior determines the fraction of EF-Tu copies that are ribosome bound. We infer simultaneous tethering of ~4 ternary complexes to the ribosome, which may facilitate rapid initial testing for codon matching on a time scale of less than 1 to 2 ms per aa-tRNA.
Molecular Insights into Function and Competitive Inhibition of
Pseudomonas aeruginosa
Multiple Virulence Factor Regulator
Authors: Kitao Tomoe , Lepine Francois , Babloudi Seda , Walte Frederick , Steinbacher Stefan , Maskos Klaus , Blaesse Michael , Negri Michele , Pucci Michael , Zahler Bob , Felici Antonio , Rahme Laurence G. 
Published: January 2018

ABSTRACT

New approaches to antimicrobial drug discovery are urgently needed to combat intractable infections caused by multidrug-resistant (MDR) bacteria.
M
ultiple
v
irulence
f
actor
r
egulator (MvfR or PqsR), a
Pseudomonas aeruginosa
quorum sensing transcription factor, regulates functions important in both acute and persistent infections. Recently identified non-ligand-based benzamine-benzimidazole (BB) inhibitors of MvfR suppress both acute and persistent
P. aeruginosa
infections in mice without perturbing bacterial growth. Here, we elucidate the crystal structure of the MvfR ligand binding domain (LBD) in complex with one potent BB inhibitor, M64. Structural analysis indicated that M64 binds, like native ligands, to the MvfR hydrophobic cavity. A hydrogen bond and pi interaction were found to be important for MvfR-M64 affinity. Surface plasmon resonance analysis demonstrated that M64 is a competitive inhibitor of MvfR. Moreover, a protein engineering approach revealed that Gln194 and Tyr258 are critical for the interaction between MvfR and M64. Random mutagenesis of the full-length MvfR protein identified a single-amino-acid substitution, I68F, at a DNA binding linker domain that confers M64 insensitivity. In the presence of M64, I68F but not the wild-type (WT) MvfR protein retained DNA binding ability. Our findings strongly suggest that M64 promotes conformational change at the DNA binding domain of MvfR and that the I68F mutation may compensate for this change, indicating allosteric inhibition. This work provides critical new insights into the molecular mechanism of MvfR function and inhibition that could aid in the optimization of anti-MvfR compounds and improve our understanding of MvfR regulation.

IMPORTANCE
Pseudomonas aeruginosa
is an opportunistic Gram-negative pathogen that causes serious acute, persistent, and relapsing infections. New approaches to antimicrobial drug discovery are urgently needed to combat intractable infections caused by this pathogen. The
Pseudomonas aeruginosa
quorum sensing transcription factor MvfR regulates functions important in both acute and persistent infections. We used recently identified inhibitors of MvfR to perform structural studies and reveal important insights that would benefit the optimization of anti-MvfR compounds. Altogether, the results reported here provide critical detailed mechanistic insights into the function of MvfR domains that may benefit the optimization of the chemical, pharmacological, and safety properties of MvfR antagonist series.
Оптимізація діагностичної програми у хворих на гостру непрохідність тонкої кишки
Authors: Dziubanovskyi I. Ya. , Benedykt V. V. 
Published: January 2018

Метою роботи: розробка ефективної і доступної діагностичної програми у хворих на ГНТК для покращення результатів їх хірургічного лікування.Матеріали і методи. У 221 пацієнта проведено комплексне обстеження з визначенням індексу коморбідності, функціонального стану хворих і ступеня операційно-анестезіологічного ризику. Ретроспективний аналіз проведено у 30 хворих із несприятливими наслідками.Результати досліджень та їх обговорення. Рентгенологічне дослідження виконано в 96,67 % померлих хворих і у всіх пацієнтів зі сприятливим перебігом захворювання. УЗД органів черевної порожнини виконано в 33,33 % і 49,77 % випадків, відповідно. Звернено увагу на значення кожного з цих методів під час обстеження хворих. При досліджені моторно-евакуаторної функції травного каналу було виявлено, що задовільна перистальтика ТК була тільки в 8 (3,62 %) випадках, її підсилення спостерігалося у 78 (35,29 %) хворих, пригнічення – у 103 (46,61 %) пацієнтів та її відсутність – у 32 (14,48 %) госпіталізованих. У хворих із несприятливим перебігом захворювання в одному випадку характер перистальтичних звуків був ритмічний, непідсилений, в 36,67 % – спостерігалося їх підсилення, пригнічення та її відсутність – в 60 % хворих. При дослідження ЛІІ та ПЛІ виявлено, що при несприятливому перебізі ГНТК ЛІІ склав (3,99 ± 0,84) од., ПЛІ – (1,21±0,33) од., у хворих при сприятливому перебізі хвороби – (4,06± 0,24) од. і (0,82 ± 0,07) од., відповідно. У 146 (66,06 %) випадках функціональний стан хворих був компенсованим і в 75 (33,94 %) випадках – декомпенсованим. Індекс коморбідності в цих хворих був наступним: до 59 роки – 1,03, у віці 60–74 роки – 4,82 і у віковій групі 75–89 роки – 6,0. У хворих з несприятливим перебігом захворювання індекс коморбідності був значно вищим, що вказувало на важливе значення супутніх захворювань у перебігу ГНТК. Запропоновано діагностичний алгоритм у хворих на ГНТК, який дозволяє проводити моніторинг перебігу захворювання і забезпечує оптимізацію хірургічної допомоги таким пацієнтам.
Клінічний випадок лейоміоми тонкої кишки
Authors: Suprunets O. L. , Suprunets B. O. , Bukata V. V. , Humennyy R. I. 
Published: January 2018

Доброякісні непітеліальні пухлини складають 25 % від всіх пухлинних захворювань тонкого кишечника,та 2,3 % всіх новоутворів шлунково-кишкового тракту. Лейоміома тонкої кишки відноситься до рідких патологій шлунково-кишкового тракту. Рідкість новоутворів тонкої кишки,пояснюють відносно малою травматизацією кишківника,високою перетравлюющою здатністю соків залозистого апарату даного відділу кишечника т та швидким пасажом вмісту. Діагностика неепітеліальних пухлин на догоспітальному періоді достатньо утруднена,оскільки пацієнти поступають в стаціонар з розвинутими ускладненнями.
Estádio do Pacaembu: do palco de emoções ao gigante sem dono
Authors: Lupo Bianca Manzon 
Published: January 2018

Propõe-se uma reflexão sobre a inserção do futebol brasileiro nas dinâmicas globais nos anos recentes, suscitando pressões pela modernização de estádios sobretudo a partir da execução de eventos internacionais no Brasil – a Copa das Confederações (2013) e a Copa do Mundo (2014). Nesse sentido, observa-se a disseminação do imaginário relacionado ao “padrão Fifa” e ao “sonho na nova arena” como desejo de representação da grandeza dos principais clubes brasileiros. Como esse contexto, entretanto, relaciona-se aos interesses associados à preservação de estádios encarados como patrimônio cultural? Para executar essa análise, emerge o caso do Estádio do Pacaembu, em São Paulo, tombado em nível municipal e estadual, que vem sendo objeto de amplas discussões nas décadas recentes. O artigo pretende aprofundar a análise desses debates, investigando em que medida as intenções de concessão e modernização do estádio, baseadas no argumento da subutilização e dos altos custos de manutenção, incidem sobre o equipamento público, encarado como patrimônio cultural. Para tanto, o estudo se desenvolverá a partir de três aspectos: analisar o Pacaembu enquanto elemento de memória e identidade de grupos sociais; verificar em que medida o interesse de sua concessão é mobilizado de acordo com as dinâmicas dos estádios paulistas e aprofundar o entendimento sobre os debates recentes travados entre órgãos de preservação, administradores públicos, associações de bairro, entre outros agentes envolvidos.
Gestão do acervo do Arquiteto Eduardo Kneese De Mello: relato do tratamento organizacional da coleção iconográfica
Authors: Santos Ademir Pereira dos , Silva Elisa Horta , Amaral Izadora Araújo 
Published: January 2018

O presente trabalho pauta-se no relato do processo de organização e catalogação primária da seção iconográfica do acervo do arquiteto Eduardo Kneese de Mello (1906–1994), realizado no ano de 2015, atualmente integrado à biblioteca do Centro Universitário Belas Artes de São Paulo. O fundo, produzido em vida pelo arquiteto, recuperou força no ano de 2006, com sua proficuidade como fonte de pesquisa anunciada pelo Dr. Ademir Pereira dos Santos, estimulando o início de diferentes manejos. Após a elucidação acerca da trajetória institucional deste material, demonstra-se aqui uma produção orientada por inquietações díspares aos trabalhos anteriores, objetivadas pela correlação da porção mais significativa do acervo, os slides, com as demais espécies documentais que compõem o conjunto do acervo. Seguinte à compreensão dos escopos que sucederam o vasto material constituinte do fundo, demonstra-se a metodologia empregada para tratamento, diagnóstico e estruturação do catálogo, assim como sua importância como base informacional, através da qual se constituiu um panorama visual e quantitativo com o auxílio e gerenciamento de tabelas descritivas, gráficos percentuais de diferentes análises e a elaboração de mapas com roteiros ilustrativos que proporcionaram a exatidão geográfica de seu conhecimento e dos testemunhos históricos. A especulação das camadas existentes possibilitou o início da confirmação de informações publicadas sobre o arquiteto e mais uma complementação de sua biografia, com o conhecimento total de suas viagens. Considerou-se como função primordial a caracterização panorâmica do conteúdo do acervo, até então desconhecida, acabando-se por evidenciar futuras problemáticas a serem enfrentadas, potencialidades e ações e intervenções urgentes e primordiais à sobrevivência do fundo.
Stroke Incidence and Outcomes in Northeastern Greece
Authors: Tsivgoulis Georgios , Patousi Athanasia , Pikilidou Maria , Birbilis Theodosis , Katsanos Aristeidis H. , Mantatzis Michalis , Asimis Aristeidis , Papanas Nikolaos , Skendros Panagiotis , Terzoudi Aikaterini , Karamanli Aikaterini , Kouroumichakis Ioannis , Zebekakis Pantelis , Maltezos Efstratios , Piperidou Charitomeni , Vadikolias Konstantinos , Heliopoulos Ioannis 
Published: January 2018

Background and Purpose—
Data are scarce on both stroke incidence rates and outcomes in Greece and in rural areas in particular. We performed a prospective population-based study evaluating the incidence of first-ever stroke in the Evros prefecture, a region of a total 147 947 residents located in North Eastern Greece.

Methods—
Adult patients with first-ever stroke were registered during a 24-month period (2010–2012) and followed up for 12 months. To compare our stroke incidence with that observed in other studies, we standardized our incidence rate data according to the European Standard Population, World Health Organization, and Segi population. We also applied criteria of data quality proposed by the Monitoring Trends and Determinants in Cardiovascular Disease project. Stroke diagnosis and classification were performed using World Health Organization criteria on the basis of neuroimaging and autopsy data.

Results—
We prospectively documented 703 stroke cases (mean age: 75±12 years; 52.8% men; ischemic stroke: 80.8%; intracerebral hemorrhage: 11.8%; subarachnoid hemorrhage: 4.4%; undefined: 3.0%) with a total follow-up time of 119 805 person-years. The unadjusted and European Standard Population–adjusted incidences of all strokes were 586.8 (95% confidence interval [CI], 543.4–630.2) and 534.1 (95% CI, 494.6–573.6) per 100 000 person-years, respectively. The unadjusted incidence rates for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 474.1 (95% CI, 435–513), 69.3 (95% CI, 54–84), and 25.9 (95% CI, 17–35) per 100 000 person-years, respectively. The corresponding European Standard Population–adjusted incidence rates per 100 000 person-years were 425.9 (95% CI, 390.9–460.9), 63.3 (95% CI, 49.7–76.9), and 25.8 (95% CI, 16.7–34.9) for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, respectively. The overall 28-day case fatality rate was 21.3% (95% CI, 18.3%–24.4%) for all strokes and was higher in hemorrhagic strokes than ischemic stroke (40.4%, 95% CI, 31.3%–49.4% versus 16.2%, 95% CI, 13.2%–19.2%).

Conclusions—
This is the largest to date population-based study in Greece documenting one of the highest stroke incidences ever reported in South Europe, highlighting the need for efficient stroke prevention and treatment strategies in Northeastern Greece.
Closure of Patent Foramen Ovale Versus Medical Therapy in Patients With Cryptogenic Stroke or Transient Ischemic Attack
Authors: Ntaios George , Papavasileiou Vasileios , Sagris Dimitrios , Makaritsis Konstantinos , Vemmos Konstantinos , Steiner Thorsten , Michel Patrik 
Published: January 2018

Background and Purpose—
Previous systematic reviews and meta-analyses compared the efficacy and safety of patent foramen ovale (PFO) closure versus medical treatment in patients with cryptogenic stroke or transient ischemic attack (TIA). Recently, new evidence from randomized trials became available.

Methods—
We searched PubMed until September 24, 2017, for trials comparing PFO closure with medical treatment in patients with cryptogenic stroke/TIA using the items: stroke or cerebrovascular accident or TIA and patent foramen ovale or paradoxical embolism and trial or study.

Results—
Among 851 identified articles, 5 were eligible. In 3627 patients with 3.7-year mean follow-up, there was significant difference in ischemic stroke recurrence (0.53 versus 1.1 per 100 patient-years, respectively; odds ratio [OR], 0.43; 95% confidence intervals (CI), 0.21–0.90; relative risk reduction, 50.5%; absolute risk reduction, 2.11%; and number needed to treat to prevent 1 event, 46.5 for 3.7 years). There was no significant difference in TIAs (0.78 versus 0.98 per 100 patient-years, respectively; OR, 0.80; 95% CI, 0.53–1.19) and all-cause mortality (0.18 versus 0.23 per 100 patient-years, respectively; OR, 0.73; 95% CI, 0.34–1.56). New-onset atrial fibrillation occurred more frequently in the PFO closure arm (1.3 versus 0.25 per 100 patient-years, respectively; OR, 5.15; 95% CI, 2.18–12.15) and resolved in 72% of cases within 45 days, whereas rates of myocardial infarction (0.12 versus 0.09 per 100 patient-years, respectively; OR, 1.22; 95% CI, 0.25–5.91) and any serious adverse events (7.3 versus 7.3 per 100 patient-years, respectively; OR, 1.07; 95% CI, 0.92–1.25) were similar.

Conclusions—
In patients with cryptogenic stroke/TIA and PFO who have their PFO closed, ischemic stroke recurrence is less frequent compared with patients receiving medical treatment. Atrial fibrillation is more frequent but mostly transient. There is no difference in TIA, all-cause mortality, or myocardial infarction.
The Jewish Unions in America
Authors: Weinstein Bernard 
Published: January 2018

Newly arrived in New York in 1882 from Tsarist Russia, the sixteen-year-old Bernard Weinstein discovered an America in which unionism, socialism, and anarchism were very much in the air. He found a home in the tenements of New York and for the next fifty years he devoted his life to the struggles of fellow Jewish workers.
The Jewish Unions in America blends memoir and history to chronicle this time. It describes how Weinstein led countless strikes, held the unions together in the face of retaliation from the bosses, investigated sweatshops and factories with the aid of reformers, and faced down schisms by various factions, including Anarchists and Communists. He co-founded the United Hebrew Trades and wrote speeches, articles and books advancing the cause of the labor movement.
From the pages of this book emerges a vivid picture of workers’ organizations at the beginning of the twentieth century and a capitalist system that bred exploitation, poverty, and inequality. Although workers’ rights have made great progress in the decades since, Weinstein’s descriptions of workers with jobs pitted against those without, and American workers against workers abroad, still carry echoes today. The Jewish Unions in America is a testament to the struggles of working people a hundred years ago. But it is also a reminder that workers must still battle to live decent lives in the free market.
For the first time, Maurice Wolfthal’s readable translation makes Weinstein’s Yiddish text available to English readers. It is essential reading for students and scholars of labor history, Jewish history, and the history of American immigration.
The Community Leveraged Unified Ensemble (CLUE) in the 2016 NOAA/Hazardous Weather Testbed Spring Forecasting Experiment
Authors: Clark Adam J. , Jirak Israel L. , Dembek Scott R. , Creager Gerry J. , Kong Fanyou , Thomas Kevin W. , Knopfmeier Kent H. , Gallo Burkely T. , Melick Christopher J. , Xue Ming , Brewster Keith A. , Jung Youngsun , Kennedy Aaron , Dong Xiquan , Markel Joshua , Gilmore Matthew , Romine Glen S. , Fossell Kathryn R. , Sobash Ryan A. , Carley Jacob R. , Ferrier Brad S. , Pyle Matthew , Alexander Curtis R. , Weiss Steven J. , Kain John S. , Wicker Louis J. , Thompson Gregory , Adams-Selin Rebecca D. , Imy David A. 
Published: January 2018

AbstractOne primary goal of annual Spring Forecasting Experiments (SFEs), which are coorganized by NOAA’s National Severe Storms Laboratory and Storm Prediction Center and conducted in the National Oceanic and Atmospheric Administration’s (NOAA) Hazardous Weather Testbed, is documenting performance characteristics of experimental, convection-allowing modeling systems (CAMs). Since 2007, the number of CAMs (including CAM ensembles) examined in the SFEs has increased dramatically, peaking at six different CAM ensembles in 2015. Meanwhile, major advances have been made in creating, importing, processing, verifying, and developing tools for analyzing and visualizing these large and complex datasets. However, progress toward identifying optimal CAM ensemble configurations has been inhibited because the different CAM systems have been independently designed, making it difficult to attribute differences in performance characteristics. Thus, for the 2016 SFE, a much more coordinated effort among many collaborators was made by agreeing on a set of model specifications (e.g., model version, grid spacing, domain size, and physics) so that the simulations contributed by each collaborator could be combined to form one large, carefully designed ensemble known as the Community Leveraged Unified Ensemble (CLUE). The 2016 CLUE was composed of 65 members contributed by five research institutions and represents an unprecedented effort to enable an evidence-driven decision process to help guide NOAA’s operational modeling efforts. Eight unique experiments were designed within the CLUE framework to examine issues directly relevant to the design of NOAA’s future operational CAM-based ensembles. This article will highlight the CLUE design and present results from one of the experiments examining the impact of single versus multicore CAM ensemble configurations.