bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic Signatures of Bacterial Adaptation to Life in the Phyllosphere of a Salt-Secreting Desert Tree
Authors: Finkel Omri M. , Delmont Tom O. , Post Anton F. , Belkin Shimshon 
Published: March 2016

ABSTRACT

The leaves of
Tamarix aphylla
, a globally distributed, salt-secreting desert tree, are dotted with alkaline droplets of high salinity. To successfully inhabit these organic carbon-rich droplets, bacteria need to be adapted to multiple stress factors, including high salinity, high alkalinity, high UV radiation, and periodic desiccation. To identify genes that are important for survival in this harsh habitat, microbial community DNA was extracted from the leaf surfaces of 10
Tamarix aphylla
trees along a 350-km longitudinal gradient. Shotgun metagenomic sequencing, contig assembly, and binning yielded 17 genome bins, six of which were >80% complete. These genomic bins, representing three phyla (
Proteobacteria
,
Bacteroidetes
, and
Firmicutes
), were closely related to halophilic and alkaliphilic taxa isolated from aquatic and soil environments. Comparison of these genomic bins to the genomes of their closest relatives revealed functional traits characteristic of bacterial populations inhabiting the
Tamarix
phyllosphere, independent of their taxonomic affiliation. These functions, most notably light-sensing genes, are postulated to represent important adaptations toward colonization of this habitat.

IMPORTANCE
Plant leaves are an extensive and diverse microbial habitat, forming the main interface between solar energy and the terrestrial biosphere. There are hundreds of thousands of plant species in the world, exhibiting a wide range of morphologies, leaf surface chemistries, and ecological ranges. In order to understand the core adaptations of microorganisms to this habitat, it is important to diversify the type of leaves that are studied. This study provides an analysis of the genomic content of the most abundant bacterial inhabitants of the globally distributed, salt-secreting desert tree
Tamarix aphylla
. Draft genomes of these bacteria were assembled, using the culture-independent technique of assembly and binning of metagenomic data. Analysis of the genomes reveals traits that are important for survival in this habitat, most notably, light-sensing and light utilization genes.
Mycelium-Like Networks Increase Bacterial Dispersal, Growth, and Biodegradation in a Model Ecosystem at Various Water Potentials
Authors: Worrich Anja , König Sara , Miltner Anja , Banitz Thomas , Centler Florian , Frank Karin , Thullner Martin , Harms Hauke , Kästner Matthias , Wick Lukas Y. 
Published: March 2016

ABSTRACT

Fungal mycelia serve as effective dispersal networks for bacteria in water-unsaturated environments, thereby allowing bacteria to maintain important functions, such as biodegradation. However, poor knowledge exists on the effects of dispersal networks at various osmotic (Ψ
o
) and matric (Ψ
m
) potentials, which contribute to the water potential mainly in terrestrial soil environments. Here we studied the effects of artificial mycelium-like dispersal networks on bacterial dispersal dynamics and subsequent effects on growth and benzoate biodegradation at ΔΨ
o
and ΔΨ
m
values between 0 and −1.5 MPa. In a multiple-microcosm approach, we used a green fluorescent protein (GFP)-tagged derivative of the soil bacterium
Pseudomonas putida
KT2440 as a model organism and sodium benzoate as a representative of polar aromatic contaminants. We found that decreasing ΔΨ
o
and ΔΨ
m
values slowed bacterial dispersal in the system, leading to decelerated growth and benzoate degradation. In contrast, dispersal networks facilitated bacterial movement at ΔΨ
o
and ΔΨ
m
values between 0 and −0.5 MPa and thus improved the absolute biodegradation performance by up to 52 and 119% for ΔΨ
o
and ΔΨ
m
, respectively. This strong functional interrelationship was further emphasized by a high positive correlation between population dispersal, population growth, and degradation. We propose that dispersal networks may sustain the functionality of microbial ecosystems at low osmotic and matric potentials.
Evaluation of Fluorescent Capillary Electrophoresis for Rapid Identification of Candida Fungal Infections
Authors: Obručová Hana , Tihelková Radka , Kotásková Iva , Růžička Filip , Holá Veronika , Němcová Eva , Freiberger Tomáš 
Published: March 2016

ABSTRACT

Early diagnosis of fungal infection is critical for initiating antifungal therapy and reducing the high mortality rate in immunocompromised patients. In this study, we focused on rapid and sensitive identification of clinically important
Candida
species, utilizing the variability in the length of the
ITS2
rRNA gene and fluorescent capillary electrophoresis (f-
ITS2
-PCR-CE). The method was developed and optimized on 29 various
Candida
reference strains from which 26
Candida
species were clearly identified, while
Candida guilliermondii
,
C. fermentati
, and
C. carpophila
, which are closely related, could not be distinguished. The method was subsequently validated on 143 blinded monofungal clinical isolates (comprising 26 species) and was able to identify 88% of species unambiguously. This indicated a higher resolution power than the classical phenotypic approach which correctly identified 73%. Finally, the culture-independent potential of this technique was addressed by the analysis of 55 retrospective DNA samples extracted directly from clinical material. The method showed 100% sensitivity and specificity compared to those of the combined results of cultivation and panfungal PCR followed by sequencing used as a gold standard. In conclusion, this newly developed f-
ITS2
-PCR-CE analytical approach was shown to be a fast, sensitive, and highly reproducible tool for both culture-dependent and culture-independent identification of clinically important
Candida
strains, including species of the “psilosis” complex.
Molecular Evolutionary Dynamics of Respiratory Syncytial Virus Group A in Recurrent Epidemics in Coastal Kenya
Authors: Otieno James R. , Agoti Charles N. , Gitahi Caroline W. , Bett Ann , Ngama Mwanajuma , Medley Graham F. , Cane Patricia A. , Nokes D. James 
Published: March 2016

ABSTRACT

The characteristic recurrent epidemics of human respiratory syncytial virus (RSV) within communities may result from the genetic variability of the virus and associated evolutionary adaptation, reducing the efficiency of preexisting immune responses. We analyzed the molecular evolutionary changes in the attachment (G) glycoprotein of RSV-A viruses collected over 13 epidemic seasons (2000 to 2012) in Kilifi (
n
= 649), Kenya, and contemporaneous sequences (
n
= 1,131) collected elsewhere within Kenya and 28 other countries. Genetic diversity in the G gene in Kilifi was dynamic both within and between epidemics, characterized by frequent new variant introductions and limited variant persistence between consecutive epidemics. Four RSV-A genotypes were detected in Kilifi: ON1 (11.9%), GA2 (75.5%), GA5 (12.3%), and GA3 (0.3%), with predominant genotype replacement of GA5 by GA2 and then GA2 by ON1. Within these genotypes, there was considerable variation in potential
N
-glycosylation sites, with GA2 and ON1 viruses showing up to 15 different patterns involving eight possible sites. Further, we identified 15 positively selected and 34 genotype-distinguishing codon sites, with six of these sites exhibiting both characteristics. The mean substitution rate of the G ectodomain for the Kilifi data set was estimated at 3.58 × 10
−3
(95% highest posterior density interval = 3.04 to 4.16) nucleotide substitutions/site/year. Kilifi viruses were interspersed in the global phylogenetic tree, clustering mostly with Kenyan and European sequences. Our findings highlight ongoing genetic evolution and high diversity of circulating RSV-A strains, locally and globally, with potential antigenic differences. Taken together, these provide a possible explanation on the nature of recurrent local RSV epidemics.

IMPORTANCE
The mechanisms underlying recurrent epidemics of RSV are poorly understood. We observe high genetic diversity in circulating strains within and between epidemics in both local and global settings. On longer time scales (∼7 years) there is sequential replacement of genotypes, whereas on shorter time scales (one epidemic to the next or within epidemics) there is a high turnover of variants within genotypes. Further, this genetic diversity is predicted to be associated with variation in antigenic profiles. These observations provide an explanation for recurrent RSV epidemics and have potential implications on the long-term effectiveness of vaccines.
Rationale, design and methodology of a trial evaluating three strategies designed to improve sedation quality in intensive care units (DESIST study)
Authors: Walsh Timothy S , Kydonaki Kalliopi , Antonelli Jean , Stephen Jacqueline , Lee Robert J , Everingham Kirsty , Hanley Janet , Uutelo Kimmo , Peltola Petra , Weir Christopher J 
Published: March 2016

ObjectivesTo describe the rationale, design and methodology for a trial of three novel interventions developed to improve sedation-analgesia quality in adult intensive care units (ICUs).Participants and Setting8 clusters, each a Scottish ICU. All mechanically ventilated sedated patients were potentially eligible for inclusion in data analysis.DesignCluster randomised design in 8 ICUs, with ICUs randomised after 45 weeks baseline data collection to implement one of four intervention combinations: a web-based educational programme (2 ICUs); education plus regular sedation quality feedback using process control charts (2 ICUs); education plus a novel sedation monitoring technology (2 ICUs); or all three interventions. ICUs measured sedation-analgesia quality, relevant drug use and clinical outcomes, during a 45-week preintervention and 45-week postintervention period separated by an 8-week implementation period. The intended sample size was >100 patients per site per study period.Main Outcome measuresThe primary outcome was the proportion of 12 h care periods with optimum sedation-analgesia, defined as the absence of agitation, unnecessary deep sedation, poor relaxation and poor ventilator synchronisation. Secondary outcomes were proportions of care periods with each of these four components of optimum sedation and rates of sedation-related adverse events. Sedative and analgesic drug use, and ICU and hospital outcomes were also measured.Analytic approachMultilevel generalised linear regression mixed models will explore the effects of each intervention taking clustering into account, and adjusting for age, gender and APACHE II score. Sedation-analgesia quality outcomes will be explored at ICU level and individual patient level. A process evaluation using mixed methods including quantitative description of intervention implementation, focus groups and direct observation will provide explanatory information regarding any effects observed.ConclusionsThe DESIST study uses a novel design to provide system-level evaluation of three contrasting complex interventions on sedation-analgesia quality. Recruitment is complete and analysis ongoing.Trial registration numberNCT01634451.
Sex differences in the effects of 12 weeks sprint interval training on body fat mass and the rates of fatty acid oxidation and VO2max during exercise
Authors: Bagley Liam , Slevin Mark , Bradburn Steven , Liu Donghui , Murgatroyd Chris , Morrissey George , Carroll Michael , Piasecki Mathew , Gilmore William S , McPhee Jamie S 
Published: March 2016

BackgroundThe purpose of this study was to examine whether very short duration, very high intensity sprint interval training (SIT) leads to loss of body fat mass in association with improvements to VO2max and fatty acid oxidation, and to assess the extent of sex dimorphism in these physiological responses.MethodsA total of 24 men and 17 women (mean (SEM) age: 39 (±2) years; body mass index 24.6 (0.6)) completed measurements of the maximal rate of oxygen uptake (VO2max) and fatty acid oxidation (FATmax). Body fat and lean mass were measured by dual emission x-ray absorptiometry, and fasting blood lipid, glucose and insulin profiles were assessed before and after training. SIT consisted of 4×20 s sprints on a cycle ergometer at approximately 175% VO2max, three times per week for 12 weeks.ResultsFat mass decreased by 1.0 kg, although men lost statistically significantly more fat than women both when expressed in Kg and as % body fat. VO2max increased by around 9%, but women improved VO2max significantly more than men. FATmax improved by around 13%, but fasting plasma glucose, insulin, total triglyceride, total cholesterol and high-density lipoprotein (HDL) did not change after training, while low-density lipoprotein decreased by 8% (p=0.028) and the HDL:Total Cholesterol ratio improved by 6%. There were no sex differences in these metabolic responses to training.ConclusionsThese results show lower body fat %, and higher rates of fatty acid oxidation and VO2max after 12 weeks of training for just 4 min per week. Notably, women improved VO2max more than men, while men lost more fat than women.
Self-reported suicide ideation and attempts, and medical care for intentional self-harm in lesbians, gays and bisexuals in Sweden
Authors: Björkenstam Charlotte , Kosidou Kyriaki , Björkenstam Emma , Dalman Christina , Andersson Gunnar , Cochran Susan 
Published: March 2016

BackgroundMinority sexual orientation is a robust risk indicator for self-reported suicidal ideation and attempts. However, little is known about patterns of medical care for intentional self-harm in this vulnerable population. We investigate sexual orientation-related differences in self-reported lifetime suicide symptoms and medical care for intentional self-harm between 1969 and 2010, including age at initial treatment and recurrence.MethodsWe used data from the Stockholm Public Health Cohort, a population-based sample of 874 lesbians/gays, 841 bisexuals and 67 980 heterosexuals, whose self-administered surveys have been linked to nationwide registers. Estimates of risk for medical care were calculated as incidence rate ratios (IRR) with 95% CIs.ResultsBoth suicidal ideation and attempts were more commonly reported by lesbian/gay and bisexual (LGB) individuals. Adjusting for risk-time and confounding, lesbians (IRR 3.8, 95% CI 2.7 to 5.4) and bisexual women (IRR 5.4, 95% CI 4.4 to 6.6) experienced elevated risk for medical care for intentional self-harm, as compared to heterosexual women. Gay men evidenced higher risk (IRR 2.1, 95% CI 1.3 to 3.4) as compared to heterosexual men. Recurrent medical care was more frequent in LGB individuals, especially in bisexual women and gay men. Lesbian and bisexual women were also younger than heterosexual women when they first received medical care for intentional self-harm.ConclusionsPositive histories of suicidal ideation, attempts and medical care for intentional self-harm, including higher levels of recurrence, are more prevalent among LGB individuals in contrast to heterosexuals. Lesbian/bisexual women evidence an earlier age of onset of treatment. Tailored prevention efforts are urgently needed.
Synergistic Activation of ERα by Estrogen and Prolactin in Breast Cancer Cells Requires Tyrosyl Phosphorylation of PAK1
Authors: Oladimeji Peter , Skerl Rebekah , Rusch Courtney , Diakonova Maria 
Published: March 2016

AbstractSerine/threonine kinase PAK1 is activated by estrogen and plays an important role in breast cancer. However, the integration of PAK1 into the estrogen response is not fully understood. In this study, we investigated the mechanisms underlying the hormone-induced activation of estrogen receptor (ERα, ESR1). We show that estrogen activated PAK1 through both the ERα and GPER1 membrane receptors. Estrogen-dependent activation of PAK1 required the phosphorylation of tyrosine residues by Etk/Bmx and protein kinase A (PKA) within an assembled signaling complex comprising pTyr-PAK1, Etk/Bmx, the heterotrimer G-protein subunits Gβ1, Gγ2, and/or Gγ5, PAK-associated guanine nucleotide exchange factor (βPIX, ARHGEF7), and PKA. Moreover, the PKA RIIβ subunit is a direct target of PAK1, and thus in response to estrogen, the activated pTyr-PAK1 complex reciprocally potentiated PKA activity, suggesting a positive feedback mechanism. We also demonstrate that PKA phosphorylated Ser305-ERα in response to estrogen, but pTyr-PAK1 phosphorylated Ser305-ERα in response to prolactin (PRL), implying that maximal ERα phosphorylation is achieved when cells are exposed to both PRL and estrogen. Furthermore, S305-ERα activation led to enhanced phosphorylation of Ser118-ERα and promoted cell proliferation and tumor growth. Together, these data strongly support a critical interplay between PRL and estrogen via PAK1 and suggest that ligand-independent activation of ERα through PRL/PAK1 may impart resistance to anti-estrogen therapies. Cancer Res; 76(9); 2600–11. ©2016 AACR.
TNF-Related Apoptosis-Inducing Ligand (TRAIL)–Armed Exosomes Deliver Proapoptotic Signals to Tumor Site
Authors: Rivoltini Licia , Chiodoni Claudia , Squarcina Paola , Tortoreto Monica , Villa Antonello , Vergani Barbara , Bürdek Maja , Botti Laura , Arioli Ivano , Cova Agata , Mauri Giorgio , Vergani Elisabetta , Bianchi Beatrice , Della Mina Pamela , Cantone Laura , Bollati Valentina , Zaffaroni Nadia , Gianni Alessandro Massimo , Colombo Mario Paolo , Huber Veronica 
Published: March 2016

Abstract
Purpose: Exosomes deliver signals to target cells and could thus be exploited as an innovative therapeutic tool. We investigated the ability of membrane TRAIL-armed exosomes to deliver proapoptotic signals to cancer cells and mediate growth inhibition in different tumor models.
Experimental Methods and Results: K562 cells, transduced with lentiviral human membrane TRAIL, were used for the production of TRAIL+ exosomes, which were studied by nanoparticle tracking analysis, cytofluorimetry, immunoelectronmicroscopy, Western blot, and ELISA. In vitro, TRAIL+ exosomes induced more pronounced apoptosis (detected by Annexin V/propidium iodide and activated caspase-3) in TRAIL-death receptor (DR)5+ cells (SUDHL4 lymphoma and INT12 melanoma), with respect to the DR5−DR4+KMS11 multiple myeloma. Intratumor injection of TRAIL+ exosomes, but not mock exosomes, induced growth inhibition of SUDHL4 (68%) and INT12 (51%), and necrosis in KMS11 tumors. After rapid blood clearance, systemically administered TRAIL+ exosomes accumulated in the liver, lungs, and spleen and homed to the tumor site, leading to a significant reduction of tumor growth (58%) in SUDHL4-bearing mice. The treatment of INT12-bearing animals promoted tumor necrosis and a not statistically significant tumor volume reduction. In KMS11-bearing mice, despite massive perivascular necrosis, no significant tumor growth inhibition was detected.
Conclusions: TRAIL-armed exosomes can induce apoptosis in cancer cells and control tumor progression in vivo. Therapeutic efficacy was particularly evident in intratumor setting, while depended on tumor model upon systemic administration. Thanks to their ability to deliver multiple signals, exosomes thus represent a promising therapeutic tool in cancer. Clin Cancer Res; 22(14); 3499–512. ©2016 AACR.
Edelfosine Promotes Apoptosis in Androgen-Deprived Prostate Tumors by Increasing ATF3 and Inhibiting Androgen Receptor Activity
Authors: Udayakumar Thirupandiyur S. , Stoyanova Radka , Shareef Mohammed M. , Mu Zhaomei , Philip Sakhi , Burnstein Kerry L. , Pollack Alan 
Published: March 2016

Abstract
Edelfosine is a synthetic alkyl-lysophospholipid that possesses significant antitumor activity in several human tumor models. Here, we investigated the effects of edelfosine combined with androgen deprivation (AD) in LNCaP and VCaP human prostate cancer cells. This treatment regimen greatly decreased cell proliferation compared with single agent or AD alone, resulting in higher levels of apoptosis in LNCaP compared with VCaP cells. Edelfosine caused a dose-dependent decrease in AKT activity, but did not affect the expression of total AKT in either cell line. Furthermore, edelfosine treatment inhibited the expression of androgen receptor (AR) and was associated with an increase in activating transcription factor 3 (ATF3) expression levels, a stress response gene and a negative regulator of AR transactivation. ATF3 binds to AR after edelfosine + AD and represses the transcriptional activation of AR as demonstrated by PSA promoter studies. Knockdown of ATF3 using siRNA-ATF3 reversed the inhibition of PSA promoter activity, suggesting that the growth inhibition effect of edelfosine was ATF3 dependent. Moreover, expression of AR variant 7 (ARv7) and TMPRSS2-ERG fusion gene were greatly inhibited after combined treatment with AD and edelfosine in VCaP cells. In vivo experiments using an orthotopic LNCaP model confirmed the antitumor effects of edelfosine + AD over the individual treatments. A significant decrease in tumor volume and PSA levels was observed when edelfosine and AD were combined, compared with edelfosine alone. Edelfosine shows promise in combination with AD for the treatment of prostate cancer patients. Mol Cancer Ther; 15(6); 1353–63. ©2016 AACR.
Heterodera glycines cysts contain an extensive array of endoproteases as well as inhibitors of proteases in H. glycines and Meloidogyne incognita infective juvenile stages
Authors: Masler Edward P. , Chitwood David J. 
Published: March 2016

Heterodera glycinescysts contain proteases, and inhibitors of protease activities in various nematode species. In this investigation, proteases inH. glycinescysts were identified using a commercially available FRET-peptide library comprising 512 peptide pools qualified to detect up to four endoprotease types (aspartic, cysteine, metallo- and serine). Native cyst content (nHglCE) digested peptides in over 96% of the pools with all four protease types identified. Serine and metalloproteases represented nearly 70% of all proteases detected and were examined further. Trypsin (serine) and matrix metalloprotease (MMP) activities were compared among nHglCE, andH. glycinessecond-stage juvenile (J2) andMeloidogyne incognitaJ2 extracts. The relative levels of activity were different for all three enzyme sources. Trypsin activity was up to 60-fold greater inM. incognitathan in eitherH. glycinessource, while MMP activity was highest in nHglCE and lowest inM. incognitaJ2. Heat-denatured cyst content (hHglCE) inhibited proteases in all three nematode preparations and was generally greater inM. incognitathan inH. glycines. Largest differences (5.2- to 6.4-fold) were observed betweenM. incognitaand nHglCE trypsin and MMP inhibition. In infective juveniles, hHglCE inhibitedM. incognitaJ2 trypsin (IC50 = 0.64 hHglCEeq reaction−1) and MMP (IC50 = 0.54) more potently than eitherH. glycinestrypsin (IC50 = 1.34) or MMP (IC50 = 1.84). Use of three MMP substrates (73, 74 and 80) revealed clear species differences as well as complex associations between activity and inhibition. MMP73 digestion rates were the same inH. glycinesandM. incognitabut responses to hHglCE inhibition were different. MMP80 digestion rates were different but inhibition was the same. MMP74 digestion rates and inhibition levels were each different between species. These experiments provide further evidence that theH. glycinescyst should be examined as a source of compounds useful for developing nematode control methods.