bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Characterization of Escherichia coli O104 Isolates from Different Sources in the United States
Authors: Rump Lydia V. , Bodeis-Jones Sonya , Abbott Jason , Zhao Shaohua , Kase Julie , Lorenz Sandra , Fischer Markus , Brown Eric , Meng Jianghong 
Published: December 2011

ABSTRACT

Escherichia coli
O104 isolates collected from different sources in the United States were examined for virulence genes typical of enterohemorrhagic
E. coli
and those identified in the O104:H4 isolate associated with the 2011 German outbreak. The unexpected presence of virulence markers in these isolates highlights the importance of screening unusual and potentially pathogenic Shiga toxin-producing
E. coli
serotypes.
Vacuolar H
+
-ATPase Works in Parallel with the HOG Pathway To Adapt Saccharomyces cerevisiae Cells to Osmotic Stress
Authors: Li Sheena Claire , Diakov Theodore T. , Rizzo Jason M. , Kane Patricia M. 
Published: December 2011

ABSTRACT

Hyperosmotic stress activates an array of cellular detoxification mechanisms, including the high-osmolarity glycerol (HOG) pathway. We report here that vacuolar H
+
-ATPase (V-ATPase) activity helps provide osmotic tolerance in
Saccharomyces cerevisiae
. V-ATPase subunit genes exhibit complex haploinsufficiency interactions with HOG pathway components.
vma
mutants lacking V-ATPase function are sensitive to high concentrations of salt and exhibit Hog1p activation even at low salt concentrations, as demonstrated by phosphorylation of Hog1p, a shift in Hog1-green fluorescent protein localization, transcriptional activation of a subset of HOG pathway effectors, and transcriptional inhibition of parallel mitogen-activated protein kinase pathway targets.
vma2Δ hog1Δ
and
vma3Δ pbs2Δ
double mutants have a synthetic growth phenotype, poor salt tolerance, and an aberrant, hyper-elongated morphology on solid media, accompanied by activation of a filamentous response element-LacZ construct, indicating cross talk into the filamentous growth pathway. Vacuoles isolated from wild-type cells briefly exposed to salt show higher levels of V-ATPase activity, and Na
+
/H
+
exchange in isolated vacuolar vesicles suggests a biochemical basis for the genetic interactions observed. V-ATPase activity is upregulated during salt stress by increasing assembly of the catalytic V
1
sector with the membrane-bound V
o
sector. Together, these data suggest that the V-ATPase acts in parallel with the HOG pathway in order to mediate salt detoxification.
Transcriptome and Functional Analysis of Mating in the Basidiomycete Schizophyllum commune
Authors: Erdmann Susann , Freihorst Daniela , Raudaskoski Marjatta , Schmidt-Heck Wolfgang , Jung Elke-Martina , Senftleben Dominik , Kothe Erika 
Published: December 2011

ABSTRACT

In this study, we undertook a functional characterization and transcriptome analysis that enabled a comprehensive study of the mating type loci of the mushroom
Schizophyllum commune
. Induced expression of both the
bar2
receptor and the
bap2(2)
pheromone gene within 6 to 12 h after mates' contact was demonstrated by quantitative real-time PCR. Similar temporal expression patterns were confirmed for the allelic
bbr1
receptor and
bbp1
pheromone-encoding genes by Northern hybridization. Interestingly, the fusion of clamp connections to the subterminal cell was delayed in mating interactions in which one of the compatible partners expressed the
bar2
receptor with a truncated C terminus. This developmental delay allowed the visualization of a green fluorescent protein (Gfp)-labeled truncated receptor at the cell periphery, consistent with a localization in the plasma membrane of unfused pseudoclamps. This finding does not support hypotheses envisioning a receptor localization to the nuclear membrane facilitating recognition between the two different nuclei present in each dikaryotic cell. Rather, Gfp fluorescence observed in such pseudoclamps indicated a role of receptor-pheromone interaction in clamp fusion. Transcriptome changes associated with mating interactions were analyzed in order to identify a role for pheromone-receptor interactions. We detected a total of 89 genes that were transcriptionally regulated in a mating type locus
A
-dependent manner, employing a cutoff of 5-fold changes in transcript abundance. Upregulation in cell cycle-related genes and downregulation of genes involved in metabolism were seen with this set of experiments. In contrast, mating type locus
B
-dependent transcriptome changes were observed in 208 genes, with a specific impact on genes related to cell wall and membrane metabolism, stress response, and the redox status of the cell.
Interplay of a Ligand Sensor and an Enzyme in Controlling Expression of the Saccharomyces cerevisiae
GAL
Genes
Authors: Abramczyk Dariusz , Holden Stacey , Page Christopher J. , Reece Richard J. 
Published: December 2011

ABSTRACT

The regulation of the
Saccharomyces cerevisiae
GAL
genes in response to galactose as a source of carbon has served as a paradigm for eukaryotic transcriptional control over the last 50 years. Three proteins—a transcriptional activator (Gal4p), an inhibitor (Gal80p), and a ligand sensor (Gal3p)—control the switch between inert and active gene expression. The molecular mechanism by which the recognition of galactose within the cell is converted into a transcriptional response has been the subject of considerable debate. In this study, using a novel and powerful method of localizing active transcription factors within the nuclei of cells, we show that a short-lived complex between Gal4p, Gal80p, and Gal3p occurs soon after the addition of galactose to cells to activate
GAL
gene expression. Gal3p is subsequently replaced in this complex by Gal1p, and a Gal4p-Gal80p-Gal1p complex is responsible for the continued expression of the
GAL
genes. The transient role of the ligand sensor indicates that current models for the induction and continued expression of the yeast
GAL
genes need to be reevaluated.
Integration of σ
B
Activity into the Decision-Making Process of Sporulation Initiation in Bacillus subtilis
Authors: Reder Alexander , Gerth Ulf , Hecker Michael 
Published: December 2011

ABSTRACT

Spo0A∼P is the master regulator of sporulation in
Bacillus subtilis
. Activity of Spo0A is regulated by a phosphorelay integrating multiple positive and negative signals by the action of kinases and phosphatases. The phosphatase Spo0E specifically inactivates the response regulator Spo0A∼P by dephosphorylation. We identified a σ
B
-type promoter adjacent to
spo0E
that is activated by the general stress response sigma factor σ
B
and is responsible for
spo0E
induction
in vivo
. Ectopic expression of σ
B
and subsequent induction of
spo0E
cause a σ
B
-dependent block of sporulation-specific transcription of the
spo0A
and
spoIIE
genes and produces a sporulation-deficient phenotype. This effect could be erased by a deletion of the σ
B
promoter of
spo0E
and thus solely addresses σ
B
activity. Here, a molecular mechanism is shown that integrates σ
B
activity into the decision-making process of sporulation and provides a link to interconnect these two dominant and probably mutually exclusive adaptive responses in the regulatory network of
B. subtilis
.
Paediatric trauma patients and attention deficit hyperactivity disorder: correlation and significance
Authors: Ertan Cem , Özcan Özlem Özel , Pepele Mustafa Safa 
Published: January 2012

IntroductionTrauma is one of the leading reasons for emergency department (ED) visits in children. Hyperactivity, inattentiveness and impulsiveness may contribute to injury proneness. The aim of this study was to evaluate the prevalence and role of attention deficit hyperactivity disorder (ADHD) in children with trauma.MethodsTrauma patients aged 3–17 attending the ED were included in the study group. Parents were informed after medical care had been given to their children, and demographic data and information about the trauma were collected. Later, parents were asked to complete the Conners' Parent Rating Scales-Revised questionnaire for ADHD symptoms. The control group consisted of children of similar age and sociocultural characteristics who attended the hospital for reasons other than trauma. Cases in which the child apparently had no active role in the trauma or where the parents did not complete the Conners' Parent Rating Scales-Revised questionnaire were excluded from the study.ResultsFifty-five children were included in the study group (mean age 7.49 (range 3–14; SD 3.3); 33 (60%) were male). The control group was statistically similar to the study group. The most common trauma mechanism was falls (n=31, 56.4%). All the subscale scores were significantly higher in the study group, and previous trauma-related ED visits were associated with significantly higher subscale scores.ConclusionThe data suggest that children who make repeated trauma-related ED visits have a predisposition to ADHD, and they may benefit from screening for this disorder while in the ED.
Data sharing for prevention: a case study in the development of a comprehensive emergency department injury surveillance system and its use in preventing violence and alcohol-related harms
Authors: Quigg Zara , Hughes Karen , Bellis Mark A 
Published: January 2012

ObjectiveTo examine emergency department (ED) data sharing via a local injury surveillance system and assess its contribution to the prevention of violence and alcohol-related harms.Methods6-year (2004–2010) exploratory study analysing injury attendances to one ED in the North West of England using descriptive and trend analyses.ResultsOver the 6-year period, there were 242 796 ED injury attendances, including 21 683 for intentional injuries. Compared with unintentional injury patients, intentional injury patients were more likely to be men, aged 18–34 years, live in the most deprived communities, have attended the ED at night/weekends, have been injured in a public place and have consumed alcohol prior to the injury. Detailed data collected on alcohol and violence-related ED attendances were shared with local partners to monitor local trends and inform prevention activity including targeted policing and licensing enforcement. Over the 6-year period, intentional ED injury attendances decreased by 35.6% and alcohol-related assault attendances decreased by 30.3%.ConclusionsThe collection of additional ED data on assault details and alcohol use prior to injury, and its integration into multi-agency policy and practice, played an important role in driving local violence prevention activity. Further research is needed to assess the direct contribution ED data sharing makes to reductions in violence.
Killing by neutrophil extracellular traps: fact or folklore?
Authors: Menegazzi Renzo , Decleva Eva , Dri Pietro 
Published: December 2011

AbstractNeutrophil extracellular traps (NETs) are DNA structures released by dying neutrophils and claimed to constitute a new microbicidal mechanism. Killing by NET-forming cells is ascribed to these structures because it is prevented by preincubation with DNase, which has been shown to dismantle NETs, before addition of the target microorganisms. Curiously, the possibility that the microorganisms ensnared in NETs are alive has not been considered. Using Staphylococcus aureus and Candida albicans blastospores, we demonstrate that the microorganisms captured by NETs and thought to be killed are alive because they are released and recovered in cell medium by incubation with DNase. It is concluded that NETs entrap but do not kill microbes.
PI3Kδ inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma
Authors: Meadows Sarah A. , Vega Francisco , Kashishian Adam , Johnson Dave , Diehl Volker , Miller Langdon L. , Younes Anas , Lannutti Brian J. 
Published: December 2011

AbstractGS-1101 (CAL-101) is an oral PI3Kδ-specific inhibitor that has shown preclinical and clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. To investigate the potential role of PI3Kδ in Hodgkin lymphoma (HL), we screened 5 HL cell lines and primary samples from patients with HL for PI3Kδ isoform expression and constitutive PI3K pathway activation. Inhibition of PI3Kδ by GS-1101 resulted in the inhibition of Akt phosphorylation. Cocultures with stroma cells induced Akt activation in HL cells, and this effect was blocked by GS-1101. Conversely, production of the stroma-stimulating chemokine, CCL5, by HL cells was reduced by GS-1101. GS-1101 also induced dose-dependent apoptosis of HL cells at 48 hours. Reductions in cell viability and apoptosis were enhanced when combining GS-1101 with the mTOR inhibitor everolimus. Our findings suggest that excessive PI3Kδ activity is characteristic in HL and support clinical evaluation of GS-1101, alone and in combination, as targeted therapy for HL.
A newly identified complex of spinophilin and the tyrosine phosphatase, SHP-1, modulates platelet activation by regulating G protein–dependent signaling
Authors: Ma Peisong , Cierniewska Aleksandra , Signarvic Rachel , Cieslak Marcin , Kong Hong , Sinnamon Andrew J. , Neubig Richard R. , Newman Debra K. , Stalker Timothy J. , Brass Lawrence F. 
Published: December 2011

Abstract
Platelets are essential for normal hemostasis, but close regulation is required to avoid the destructive effects of either inappropriate platelet activation or excessive responses to injury. Here, we describe a novel complex comprising the scaffold protein, spinophilin (SPL), and the tyrosine phosphatase, SHP-1, and show that it can modulate platelet activation by sequestering RGS10 and RGS18, 2 members of the regulator of G protein signaling family. We also show that SPL/RGS/SHP1 complexes are present in resting platelets where constitutive phosphorylation of SPL(Y398) creates an atypical binding site for SHP-1. Activation of the SHP-1 occurs on agonist-induced phosphorylation of SHP-1(Y536), triggering dephosphorylation and decay of the SPL/RGS/SHP1 complex. Preventing SHP-1 activation blocks decay of the complex and produces a gain of function. Conversely, deleting spinophilin in mice inhibits platelet activation. It also attenuates the rise in platelet cAMP normally caused by endothelial prostacyclin (PGI2). Thus, we propose that the role of the SPL/RGS/SHP1 complex in platelets is time and context dependent. Before injury, the complex helps maintain the quiescence of circulating platelets by maximizing the impact of PGI2. After injury, the complex gradually releases RGS proteins, limiting platelet activation and providing a mechanism for temporal coordination of pro thrombotic and antithrombotic inputs.
Selection of optimal alternative graft source: mismatched unrelated donor, umbilical cord blood, or haploidentical transplant
Authors: Ballen Karen K. , Koreth John , Chen Yi-Bin , Dey Bimalangshu R. , Spitzer Thomas R. 
Published: December 2011

Abstract
Only 30% of patients who require an allogeneic hematopoietic cell transplant will have an HLA-matched sibling donor. A search for an unrelated donor will be undertaken for patients without a matched family donor. However, many patients, particularly patients of diverse racial and ethnic backgrounds, may not be able to rapidly identify a suitably matched unrelated donor. Three alternative graft sources, umbilical cord blood (UCB), haploidentical (haplo)–related donor, and mismatched unrelated donor (MMUD) are available. UCB is associated with decreased GVHD, but hematologic recovery and immune reconstitution are slow. Haplo-HCT is characterized by donor availability for transplantation and after transplantation adoptive cellular immunotherapy but may be complicated by a high risk of graft failure and relapse. A MMUD transplant may also be an option, but GVHD may be of greater concern. Phase 2 studies have documented advances in HLA typing, GVHD prophylaxis, and infection prevention, which have improved survival. The same patient evaluated in different transplant centers may be offered MMUD, UCB, or haplo-HCT depending on center preference. In this review, we discuss the rationale for donor choice and the need of phase 3 studies to help answer this important question.
Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma
Authors: Kridel Robert , Meissner Barbara , Rogic Sanja , Boyle Merrill , Telenius Adele , Woolcock Bruce , Gunawardana Jay , Jenkins Christopher , Cochrane Chris , Ben-Neriah Susana , Tan King , Morin Ryan D. , Opat Stephen , Sehn Laurie H. , Connors Joseph M. , Marra Marco A. , Weng Andrew P. , Steidl Christian , Gascoyne Randy D. 
Published: December 2011

Abstract
Mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma, is characterized by the hallmark translocation t(11;14)(q13;q32) and the resulting overexpression of cyclin D1 (CCND1). Our current knowledge of this disease encompasses frequent secondary cytogenetic aberrations and the recurrent mutation of a handful of genes, such as TP53, ATM, and CCND1. However, these findings insufficiently explain the biologic underpinnings of MCL. Here, we performed whole transcriptome sequencing on a discovery cohort of 18 primary tissue MCL samples and 2 cell lines. We found recurrent mutations in NOTCH1, a finding that we confirmed in an extension cohort of 108 clinical samples and 8 cell lines. In total, 12% of clinical samples and 20% of cell lines harbored somatic NOTCH1 coding sequence mutations that clustered in the PEST domain and predominantly consisted of truncating mutations or small frame-shifting indels. NOTCH1 mutations were associated with poor overall survival (P = .003). Furthermore, we showed that inhibition of the NOTCH pathway reduced proliferation and induced apoptosis in 2 MCL cell lines. In summary, we have identified recurrent NOTCH1 mutations that provide the preclinical rationale for therapeutic inhibition of the NOTCH pathway in a subset of patients with MCL.
Genesis of a novel Shigella flexneri serotype by sequential infection of serotype-converting bacteriophages SfX and SfI
Authors: Sun Qiangzheng , Lan Ruiting , Wang Yiting , Wang Jianping , Luo Xia , Zhang Shaomin , Li Peijing , Wang Yan , Ye Changyun , Jing Huaiqi , Xu Jianguo 
Published: December 2011

Abstract

Background

Shigella flexneri is the major pathogen causing bacillary dysentery. Fifteen serotypes have been recognized up to now. The genesis of new S. flexneri serotypes is commonly mediated by serotype-converting bacteriophages. Untypeable or novel serotypes from natural infections had been reported worldwide but have not been generated in laboratory.

Results
A new S. flexneri serotype-serotype 1 d was generated when a S. flexneri serotype Y strain (native LPS) was sequentially infected with 2 serotype-converting bacteriophages, SfX first and then SfI. The new serotype 1 d strain agglutinated with both serotype X-specific anti-7;8 grouping serum and serotype 1a-specific anti- I typing serum, and differed from subserotypes 1a, 1b and 1c. Twenty four S. flexneri clinical isolates of serotype X were all converted to serotype 1 d by infection with phage SfI. PCR and sequencing revealed that SfI and SfX were integrated in tandem into the proA-yaiC region of the host chromosome.

Conclusions
These findings suggest a new S. flexneri serotype could be created in nature. Such a conversion may be constrained by susceptibility of a strain to infection by a given serotype-converting bacteriophage. This finding has significant implications in the emergence of new S. flexneri serotypes in nature.
The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring
Authors: Song Xueqin , Li Wenqiang , Yang Yongfeng , Zhao Jingping , Jiang Chengdi , Li Wei , Lv Luxian 
Published: December 2011

Abstract

Background
Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C) treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia.

Methods
We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) levels was determined by enzyme-linked immunosorbent assays (ELISA). The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI), passive avoidance, and active avoidance tests.

Results
PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring.

Conclusions
Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.
PET/CT aids the staging of and radiotherapy planning for early-stage extranodal natural killer/T-cell lymphoma, nasal type: A case series
Authors: MacDonald Shannon L , Mulroy Liam , Wilke Derek R , Burrell Steven 
Published: December 2011

Abstract
Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare form of non-Hodgkin lymphoma. Treatment of ENKTL primarily relies on radiation; thus, proper delineation of target volumes is critical. Currently, the ideal modalities for delineation of gross tumor volume for ENKTL are unknown. We describe three consecutive cases of localized ENKTL that presented to the Nova Scotia Cancer Centre in Halifax, Nova Scotia. All patients had a planning CT and MRI as well as a planning FDG-PET/CT in the radiotherapy treatment position, wearing immobilization masks. All patients received radiation alone. In two patients, PET/CT changed not only the stage, but also the target volume requiring treatment. The third patient was unable to tolerate an MRI, but was able to undergo PET/CT, which improved the accuracy of the target volume. PET/CT aided the staging of and radiotherapy planning for our patients and appears to be a promising tool in the treatment of ENKTL.
Virus Capsid Coating of Gold Nanoparticles via Cysteine–Au Interactions and Their Effective Cellular Uptakes
Authors: Nagakawa Keita , Niikura Kenichi , Suzuki Tadaki , Matsuo Yasutaka , Igarashi Manabu , Sawa Hirofumi , Ijiro Kuniharu 
Published: January 2012

Abstract
This manuscript describes the synthesis of virus capsid protein-coated Au nanoparticle (VP–AuNP) without the use of the inherent self-assembly of virus proteins into virus particles. Covalent binding between Au and cysteines in the virus proteins keep the cell-surface binding sites on the external surface. Based on this method, various sizes of VP–AuNP can be created in a similar manner to native virus particles. We clarified the optimum size of the VP–AuNP for internalization into cells.