bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent Transcriptional Responses to Physiological and Xenobiotic Stress in Giardia duodenalis
Authors: Ansell Brendan R. E. , McConville Malcolm J. , Baker Louise , Korhonen Pasi K. , Emery Samantha J. , Svärd Staffan G. , Gasser Robin B. , Jex Aaron R. 
Published: July 2016

ABSTRACT

Understanding how parasites respond to stress can help to identify essential biological processes.
Giardia duodenalis
is a parasitic protist that infects the human gastrointestinal tract and causes 200 to 300 million cases of diarrhea annually. Metronidazole, a major antigiardial drug, is thought to cause oxidative damage within the infective trophozoite form. However, treatment efficacy is suboptimal, due partly to metronidazole-resistant infections. To elucidate conserved and stress-specific responses, we calibrated sublethal metronidazole, hydrogen peroxide, and thermal stresses to exert approximately equal pressure on trophozoite growth and compared transcriptional responses after 24 h of exposure. We identified 252 genes that were differentially transcribed in response to all three stressors, including glycolytic and DNA repair enzymes, a mitogen-activated protein (MAP) kinase, high-cysteine membrane proteins, flavin adenine dinucleotide (FAD) synthetase, and histone modification enzymes. Transcriptional responses appeared to diverge according to physiological or xenobiotic stress. Downregulation of the antioxidant system and α-giardins was observed only under metronidazole-induced stress, whereas upregulation of GARP-like transcription factors and their subordinate genes was observed in response to hydrogen peroxide and thermal stressors. Limited evidence was found in support of stress-specific response elements upstream of differentially transcribed genes; however, antisense derepression and differential regulation of RNA interference machinery suggest multiple epigenetic mechanisms of transcriptional control.
Complete Genome Sequences of Three Outbreak-Associated
Legionella pneumophila
Isolates
Authors: Morrison Shatavia S. , Desai Heta P. , Mercante Jeffrey W. , Lapierre Pascal , Raphael Brian H. , Musser Kimberlee , Winchell Jonas M. 
Published: July 2016

ABSTRACT

We report here the complete genome sequences of three
Legionella pneumophila
isolates that are associated with a Legionnaires' disease outbreak in New York in 2012. Two clinical isolates (D7630 and D7632) and one environmental isolate (D7631) were recovered from this outbreak. A single isolate-specific virulence gene was found in D7632. These isolates were included in a large study evaluating the genomic resolution of various bioinformatics approaches for
L. pneumophila
serogroup 1 isolates.
Role of Serum Amyloid A, Granulocyte-Macrophage Colony-Stimulating Factor, and Bone Marrow Granulocyte-Monocyte Precursor Expansion in Segmented Filamentous Bacterium-Mediated Protection from Entamoeba histolytica
Authors: Burgess Stacey L. , Saleh Mahmoud , Cowardin Carrie A. , Buonomo Erica , Noor Zannatun , Watanabe Koji , Abhyankar Mayuresh , Lajoie Stephane , Wills-Karp Marsha , Petri William A. 
Published: July 2016

ABSTRACT

Intestinal segmented filamentous bacteria (SFB) protect from ameba infection, and protection is transferable with bone marrow dendritic cells (BMDCs). SFB cause an increase in serum amyloid A (SAA), suggesting that SAA might mediate SFB's effects on BMDCs. Here we further explored the role of bone marrow in SFB-mediated protection. Transient gut colonization with SFB or SAA administration alone transiently increased the H3K27 histone demethylase Jmjd3, persistently increased bone marrow
Csf2ra
expression and granulocyte monocyte precursors (GMPs), and protected from ameba infection. Pharmacologic inhibition of Jmjd3 H3K27 demethylase activity during SAA treatment or blockade of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling in SFB-colonized mice prevented GMP expansion, decreased gut neutrophils, and blocked protection from ameba infection. These results indicate that alteration of the microbiota and systemic exposure to SAA can influence myelopoiesis and susceptibility to amebiasis via epigenetic mechanisms. Gut microbiota-marrow communication is a previously unrecognized mechanism of innate protection from infection.
The SaeRS Two-Component System Is a Direct and Dominant Transcriptional Activator of Toxic Shock Syndrome Toxin 1 in Staphylococcus aureus
Authors: Baroja Miren L. , Herfst Christine A. , Kasper Katherine J. , Xu Stacey X. , Gillett Daniel A. , Li Jingru , Reid Gregor , McCormick John K. 
Published: July 2016

ABSTRACT

Toxic shock syndrome toxin 1 (TSST-1) is a
Staphylococcus aureus
superantigen that has been implicated in both menstrual and nonmenstrual toxic shock syndrome (TSS). Despite the important role of TSST-1 in severe human disease, a comprehensive understanding of staphylococcal regulatory factors that control TSST-1 expression remains incomplete. The
S. aureus
exotoxin expression (Sae) operon contains a well-characterized two-component system that regulates a number of important exotoxins in
S. aureus
, although regulation of TSST-1 by the Sae system has not been investigated. We generated a defined deletion mutant of the Sae histidine kinase sensor (
saeS
) in the prototypic menstrual TSS strain
S. aureus
MN8. Mutation of
saeS
resulted in a complete loss of TSST-1 expression. Using both luciferase reporter experiments and quantitative real-time PCR, we demonstrate that the Sae system is an important transcriptional activator of TSST-1 expression. Recombinant SaeR was able to bind directly to the
tst
promoter to a region containing two SaeR consensus binding sites. Although the stand-alone SarA transcriptional regulator has been shown to be both a positive and a negative regulator of TSST-1, deletion of
sarA
in
S. aureus
MN8 resulted in a dramatic overexpression of TSST-1. As expected, mutation of
agr
also reduced TSST-1 expression, but this phenotype appeared to be independent of Sae. A double mutation of
saeS
and
sarA
resulted in the loss of TSST-1 expression. This work indicates that the Sae system is a dominant and direct transcriptional activator that is required for expression of TSST-1.

IMPORTANCE
The TSST-1 superantigen is an exotoxin, produced by some strains of
S. aureus
, that has a clear role in both menstrual and nonmenstrual TSS. Although the well-characterized
agr
quorum sensing system is a known positive regulator of TSST-1, the molecular mechanisms that directly control TSST-1 expression are only partially understood. Our studies demonstrate that the Sae two-component regulatory system is a positive transcriptional regulator that binds directly to the TSST-1 promoter, and furthermore, our data suggest that Sae is required for expression of TSST-1. This work highlights how major regulatory circuits can converge to fine-tune exotoxin expression and suggests that the Sae regulatory system may be an important target for antivirulence strategies.
Complementation of Cobalamin Auxotrophy in Synechococcus sp. Strain PCC 7002 and Validation of a Putative Cobalamin Riboswitch
In Vivo
Authors: Pérez Adam A. , Liu Zhenfeng , Rodionov Dmitry A. , Li Zhongkui , Bryant Donald A. 
Published: July 2016

ABSTRACT

The euryhaline cyanobacterium
Synechococcus
sp. strain PCC 7002 has an obligate requirement for exogenous vitamin B
12
(cobalamin), but little is known about the roles of this compound in cyanobacteria. Bioinformatic analyses suggest that only the terminal enzyme in methionine biosynthesis, methionine synthase, requires cobalamin as a coenzyme in
Synechococcus
sp. strain PCC 7002. Methionine synthase (MetH) catalyzes the transfer of a methyl group from
N
5
-methyl-5,6,7,8-tetrahydrofolate to
l
-homocysteine during
l
-methionine synthesis and uses methylcobalamin as an intermediate methyl donor. Numerous bacteria and plants alternatively employ a cobalamin-independent methionine synthase isozyme, MetE, that catalyzes the same methyl transfer reaction as MetH but uses
N
5
-methyl-5,6,7,8-tetrahydrofolate directly as the methyl donor. The cobalamin auxotrophy of
Synechococcus
sp. strain PCC 7002 was complemented by using the
metE
gene from the closely related cyanobacterium
Synechococcus
sp. strain PCC 73109, which possesses genes for both methionine synthases. This result suggests that methionine biosynthesis is probably the sole use of cobalamin in
Synechococcus
sp. strain PCC 7002. Furthermore, a cobalamin-repressible gene expression system was developed in
Synechococcus
sp. strain PCC 7002 that was used to validate the presence of a cobalamin riboswitch in the promoter region of
metE
from
Synechococcus
sp. strain PCC 73109. This riboswitch acts as a cobalamin-dependent transcriptional attenuator for
metE
in that organism.

IMPORTANCE
Synechococcus
sp. strain PCC 7002 is a cobalamin auxotroph because, like eukaryotic marine algae, it uses a cobalamin-dependent methionine synthase (MetH) for the final step of
l
-methionine biosynthesis but cannot synthesize cobalamin
de novo
. Heterologous expression of
metE
, encoding cobalamin-independent methionine synthase, from
Synechococcus
sp. strain PCC 73109, relieved this auxotrophy and enabled the construction of a truly autotrophic
Synechococcus
sp. strain PCC 7002 more suitable for large-scale industrial applications. Characterization of a cobalamin riboswitch expands the genetic toolbox for
Synechococcus
sp. strain PCC 7002 by providing a cobalamin-repressible expression system.
Stair climbing/descending exercise for a short time decreases blood glucose levels after a meal in people with type 2 diabetes
Authors: Honda Hiroto , Igaki Makoto , Hatanaka Yuki , Komatsu Motoaki , Tanaka Shin-ichiro , Miki Tetsuo , Suzuki Taiga , Takaishi Tetsuo , Hayashi Tatsuya 
Published: July 2016

ObjectiveWe examined whether stair climbing–descending exercise (ST-EX), a convenient method to increase physical activity in daily life, for a short period would acutely improve the postprandial blood glucose (BG) response in people with type 2 diabetes (T2D).Methods16 people with T2D (age 65.4±1.1 years) participated in 2 separate sessions. After an overnight fast, each participant consumed a test meal and then kept resting for 180 min, except when performing each 3 min bout of ST-EX at 60 and 120 min after the meal (ST-EX session), or kept resting for 180 min (REST session). ST-EX comprised 6 continuous repetitions of climbing to the second floor (21 steps) at a rate of 80–110 steps/min followed by walking down slowly to the first floor at a free step rate.ResultsThe BG at 60 min after the meal during the ST-EX session (immediately before the first ST-EX) did not differ from that during the REST session, but analysis of variance revealed a significant interaction between time and treatment (p<0.01). The BG at 150 min after the meal (30 min after the second ST-EX) was significantly lower than that during the REST session (p<0.01). The area under the curve was also 18% lower during the ST-EX session than during the REST session (p<0.05). The heart rate and blood lactate levels indicated that the actual intensity of ST-EX was ‘hard’. In contrast, the rating of perceived exertion (RPE) indicated that the overall intensity of ST-EX was ‘moderate’ because of decreased RPE scores during descent.ConclusionsThe present findings suggest that performing 3 min ST-EX 60 and 120 min after a meal may be a useful strategy to accelerate the decrease in postprandial BG levels in people with T2D.
Pilot study to test the feasibility of a trial design and complex intervention onPRIoritisingMUltimedication inMultimorbidity in general practices (PRIMUMpilot)
Authors: Muth Christiane , Harder Sebastian , Uhlmann Lorenz , Rochon Justine , Fullerton Birgit , Güthlin Corina , Erler Antje , Beyer Martin , van den Akker Marjan , Perera Rafael , Knottnerus André , Valderas Jose M , Gerlach Ferdinand M , Haefeli Walter E 
Published: July 2016

ObjectiveTo improve medication appropriateness and adherence in elderly patients with multimorbidity, we developed a complex intervention involving general practitioners (GPs) and their healthcare assistants (HCA). In accordance with the Medical Research Council guidance on developing and evaluating complex interventions, we prepared for the main study by testing the feasibility of the intervention and study design in a cluster randomised pilot study.Setting20 general practices in Hesse, Germany.Participants100 cognitively intact patients ≥65 years with ≥3 chronic conditions, ≥5 chronic prescriptions and capable of participating in telephone interviews; 94 patients completed the study.InterventionThe HCA conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision-support system (CDSS), the GPs discussed medication intake with patients and adjusted their medication regimens. The control group continued with usual care.Outcome measuresFeasibility of the intervention and required time were assessed for GPs, HCAs and patients using mixed methods (questionnaires, interviews and case vignettes after completion of the study). The feasibility of the study was assessed concerning success of achieving recruitment targets, balancing cluster sizes and minimising drop-out rates. Exploratory outcomes included the medication appropriateness index (MAI), quality of life, functional status and adherence-related measures. MAI was evaluated blinded to group assignment, and intra-rater/inter-rater reliability was assessed for a subsample of prescriptions.Results10 practices were randomised and analysed per group. GPs/HCAs were satisfied with the interventions despite the time required (35/45 min/patient). In case vignettes, GPs/HCAs needed help using the CDSS. The study made no patients feel uneasy. Intra-rater/inter-rater reliability for MAI was excellent. Inclusion criteria were challenging and potentially inadequate, and should therefore be adjusted. Outcome measures on pain, functionality and self-reported adherence were unfeasible due to frequent missing values, an incorrect manual or potentially invalid results.ConclusionsIntervention and trial design were feasible. The pilot study revealed important limitations that influenced the design and conduct of the main study, thus highlighting the value of piloting complex interventions.Trial registration numberISRCTN99691973; Results.
On the histogenesis of mixed germ cell-sex cord stromal tumour of the gonads
Authors: Roth Lawrence M , Cheng Liang 
Published: July 2016

AimsThe origin of testicular mixed germ cell-sex cord stromal tumour (MGC-SCST) is uncertain, and the nature of this neoplasm is controversial. It has not been established whether the germ cells in testicular MGC-SCST are neoplastic or whether they are merely entrapped within an unclassified sex cord stromal tumour or related testicular neoplasm. In this investigation, we present additional evidence regarding the nature of the germ cells in testicular MGC-SCST.MethodsWe obtained 25 cases of MGC-SCST, 13 of which involved the testis and 12 occurred in the ovary for histological examination. Although the majority of the cases studied were archival, materials were available for immunocytochemical examination in 10 instances.ResultsWe found that 10 of 13 testicular MGC-SCSTs studied had a sex cord component resembling unclassified sex cord stromal tumour. In two MGC-SCSTs that had prominent entrapped tubules, an intratubular component was identified. A total of 12 ovarian MGC-SCSTs were examined, and these neoplasms were more diverse in their histological appearance than the testicular examples. The germ cells often resembled those of dysgerminoma. Formation of imperfect follicular-like structures was a frequent feature in ovarian cases.ConclusionsIn this investigation, we provide further evidence that the germ cells in testicular MGC-SCSTs are neoplastic; however, in the great majority of tumours, these cells are low-grade. Some testicular MGC-SCSTs arise from an intratubular component. We believe that the majority of ovarian and some testicular MGC-SCSTs arise more directly from simultaneous transformation of germ cells and sex cord derivatives.
Taxonomic bias and international biodiversity conservation research
Authors: Donaldson Michael R. , Burnett Nicholas J. , Braun Douglas C. , Suski Cory D. , Hinch Scott G. , Cooke Steven J. , Kerr Jeremy T. 
Published: July 2016

While greater research on threatened species alone cannot ensure their protection, understanding taxonomic bias may be helpful to address knowledge gaps in order to identify research directions and inform policy. Using data for over 10 000 animal species listed on the International Union for Conservation of Nature Red List, we investigated taxonomic and geographic biodiversity conservation research trends worldwide. We found extreme bias in conservation research effort on threatened vertebrates compared with lesser-studied invertebrates in both terrestrial and aquatic habitats at a global scale. Based on an analysis of common threats affecting vertebrates and invertebrates, we suggest a path forward for narrowing the research gap between threatened vertebrates and invertebrates.
Linear complexity of generalized cyclotomic binary sequences of order 2d and length 2pm
Authors: Zuo Xuewu , Li Xu , Xiao Jin , Tang Yuanyan , Abbasi Rashid , Xu Lixiang 
Published: July 2016

In this paper, we construct two new cyclotomic binary sequences of order [Formula: see text] and length [Formula: see text] which include the sequences constructed by Ke et al. in 2012. We also compute their linear complexity. The results show that these sequences have good linear complexity.
Receptor Tyrosine Kinase Phosphorylation Pattern–Based Multidrug Combination Is an Effective Approach for Personalized Cancer Treatment
Authors: Sun Xiaoxiao , Song Qiaoling , He Li , Yan Lei , Liu Jingli , Zhang Qing , Yu Qiang 
Published: July 2016

Abstract
Receptor tyrosine kinases (RTK) are key signaling molecules in regulating cancer cell growth and are important cancer drug targets. Despite the success of specific RTK-targeting therapy in certain cancer treatments, the overall response rates are limited to the drug target–stratified populations. We have systematically studied RTK activations in a panel of cancer cell lines, primary cancers, and cancer xenografts and found that different combinations of RTKs were activated in different cancer cells regardless of their tissue origins. Combinations of specific RTK inhibitors (RTKi) preferentially inhibited proliferation of the cancer cells with corresponding RTK activation profiles. We also found that the activations of RTKs were regulated by both cell-autonomous and environment-dependent mechanisms and demonstrated that inhibition of all activated RTKs was essential to completely block cancer cell proliferation. In addition, c-Myc downregulation was identified as an indicator for the effectiveness of the RTKi combination treatments. Our findings demonstrated that the RTK activation profile is a valid biomarker for diagnosis and stratification of cancers, and a corresponding combination of RTKis is a promising strategy to treat cancers, particularly the single RTKi therapy–resistant cancers, selectively and effectively. Mol Cancer Ther; 15(10); 2508–20. ©2016 AACR.
Abstract 10: Silibinin exhibits anti-cachectic and anti-cancerous property by modulating metabolic properties of pancreatic cancer cells
Authors: Shukla Surendra K. , Dasgupta Aneesha , Mehla Kamiya , Gunda Venugopal , Vernucci Enza , Soucheck Joshua , Goode Gennifer , King Ryan , Mishra Anusha , Rai Ibha , Natrajan Sangeetha , Chaika Nina , Yu Fang , Singh Pankaj K. 
Published: July 2016

Abstract
Cancer cachexia is a systemic syndrome characterized by progressive weight loss of the patient due to muscle wasting and fat depletion with or without anorexia. About 80% of pancreatic ductal adenocarcinoma (PDAC) patients exhibits cachectic phenotype and it significantly contributes in mortality and morbidity of the disease. In present study we have evaluated the effect of bioactive molecule silibinin on pancreatic cancer progression and cachectic properties by utilizing in vitro as well as in vivo models of PDAC. We observed that silibinin inhibits growth and induces apoptosis in multiple pancreatic cancer cell lines in a dose-dependent manner. We also observed silibinin-mediated reduction in the expression of key glycolytic genes and inhibition of glucose uptake and lactate secretion. By performing LC-MS/MS based metabolomics, we observed that silibinin treatment leads to global metabolic alterations in pancreatic cancer cells. Pancreatic cancer cells treated with silibinin exhibited reduced expression of c-MYC level, a key metabolic regulator. Furthermore, we observed that silibinin-mediated STAT3 inhibition leads to reduced c-MYC expression. Ectopic expression of constitutively active STAT3 significantly attenuated the effect of silibinin on c-MYC expression and metabolic phenotype of pancreatic cancer cells. Silibinin treatment also inhibited tumor growth and progression of cachexia. Silibinin treatment to tumor-bearing mice also lead to increased food intake, increased grip strength and body coordination. Overall, our results demonstrate that silibinin exhibits anti-cachectic and anti-cancerous properties by inducing metabolic reprogramming in pancreatic cancer cells.
Citation Format: Surendra K. Shukla, Aneesha Dasgupta, Kamiya Mehla, Venugopal Gunda, Enza Vernucci, Joshua Soucheck, Gennifer Goode, Ryan King, Anusha Mishra, Ibha Rai, Sangeetha Natrajan, Nina Chaika, Fang Yu, Pankaj K. Singh. Silibinin exhibits anti-cachectic and anti-cancerous property by modulating metabolic properties of pancreatic cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 10.