bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Phosphate Transport System Component PstB1 in Phosphate Internalization by Nostoc punctiforme
Authors: Hudek L. , Premachandra D. , Webster W. A. J. , Bräu L. 
Published: August 2016

ABSTRACT

In bacteria, limited phosphate availability promotes the synthesis of active uptake systems, such as the Pst phosphate transport system. To understand the mechanisms that facilitate phosphate accumulation in the cyanobacterium
Nostoc punctiforme
, phosphate transport systems were identified, revealing a redundancy of Pst phosphate uptake systems that exists across three distinct operons. Four separate PstB system components were identified.
pstB1
was determined to be a suitable target for creating phenotypic mutations that could result in the accumulation of excessive levels of phosphate through its overexpression or in a reduction of the capacity to accumulate phosphate through its deletion. Using quantitative real-time PCR (qPCR), it was determined that
pstB1
mRNA levels increased significantly over 64 h in cells cultured in 0 mM added phosphate and decreased significantly in cells exposed to high (12.8 mM) phosphate concentrations compared to the level in cells cultured under normal (0.8 mM) conditions. Possible compensation for the loss of PstB1 was observed when
pstB2
,
pstB3
, and
pstB4
mRNA levels increased, particularly in cells starved of phosphate. The overexpression of
pstB1
increased phosphate uptake by
N. punctiforme
and was shown to functionally complement the loss of PstB in
E. coli
PstB knockout (PstB
−
) mutants. The knockout of
pstB1
in
N. punctiforme
did not have a significant effect on cellular phosphate accumulation or growth for the most part, which is attributed to the compensation for the loss of PstB1 by alterations in the
pstB2
,
pstB3
, and
pstB4
mRNA levels. This study provides novel
in vivo
evidence that PstB1 plays a functional role in phosphate uptake in
N. punctiforme
.

IMPORTANCE
Cyanobacteria have been evolving over 3.5 billion years and have become highly adept at growing under limiting nutrient levels. Phosphate is crucial for the survival and prosperity of all organisms. In bacteria, limited phosphate availability promotes the synthesis of active uptake systems. The Pst phosphate transport system is one such system, responsible for the internalization of phosphate when cells are in phosphate-limited environments. Our investigations reveal the presence of multiple Pst phosphate uptake systems that exist across three distinct operons in
Nostoc punctiforme
and functionally characterize the role of the gene product PstB1 as being crucial for the maintenance of phosphate accumulation. We demonstrate that the genes
pstB2
,
pstB3
, and
pstB4
show alterations in expression to compensate for the deletion of
pstB1
. The overall outcomes of this work provide insights as to the complex transport mechanisms that exist in cyanobacteria like
N. punctiforme
, allowing them to thrive in low-phosphate environments.
Population Genetics of Hirsutella rhossiliensis, a Dominant Parasite of Cyst Nematode Juveniles on a Continental Scale
Authors: Wang Niuniu , Zhang Yongjie , Jiang Xianzhi , Shu Chi , Hamid M. Imran , Hussain Muzammil , Chen Senyu , Xu Jianping , Xiang Meichun , Liu Xingzhong 
Published: August 2016

ABSTRACT

Hirsutella rhossiliensis
is a parasite of juvenile nematodes, effective against a diversity of plant-parasitic nematodes. Its global distribution on various nematode hosts and its genetic variation for several geographic regions have been reported, while the global population genetic structure and factors underlying patterns of genetic variation of
H. rhossiliensis
are unclear. In this study, 87
H. rhossiliensis
strains from five nematode species (
Globodera
sp.,
Criconemella xenoplax
,
Rotylenchus robustus
,
Heterodera schachtii
, and
Heterodera glycines
) in Europe, the United States, and China were investigated by multilocus sequence analyses. A total of 280 variable sites (frequency, 0.6%) at eight loci and six clustering in high accordance with geographic populations or host nematode-associated populations were identified. Although
H. rhossiliensis
is currently recognized as an asexual fungus, recombination events were frequently detected. In addition, significant genetic isolation by geography and nematode hosts was revealed. Overall, our analyses showed that recombination, geographic isolation, and nematode host adaptation have played significant roles in the evolutionary history of
H. rhossiliensis
.

IMPORTANCE
H. rhossiliensis
has great potential for use as a biocontrol agent to control nematodes in a sustainable manner as an endoparasitic fungus. Therefore, this study has important implications for the use of
H. rhossiliensis
as a biocontrol agent and provides interesting insights into the biology of this species.
Borneol Dehydrogenase from Pseudomonas sp. Strain TCU-HL1 Catalyzes the Oxidation of (+)-Borneol and Its Isomers to Camphor
Authors: Tsang Hoi-Lung , Huang Jui-Lin , Lin Yu-Hsuan , Huang Kai-Fa , Lu Pei-Luen , Lin Guang-Huey , Khine Aye Aye , Hu Anren , Chen Hao-Ping 
Published: August 2016

ABSTRACT

Most plant-produced monoterpenes can be degraded by soil microorganisms. Borneol is a plant terpene that is widely used in traditional Chinese medicine. Neither microbial borneol dehydrogenase (BDH) nor a microbial borneol degradation pathway has been reported previously. One borneol-degrading strain,
Pseudomonas
sp. strain TCU-HL1, was isolated by our group. Its genome was sequenced and annotated. The genome of TCU-HL1 consists of a 6.2-Mbp circular chromosome and one circular plasmid, pTHL1 (12.6 kbp). Our results suggest that borneol is first converted into camphor by BDH in TCU-HL1 and is further decomposed through a camphor degradation pathway. The recombinant BDH was produced in the form of inclusion bodies. The apparent

K
m

values of refolded recombinant BDH for (+)-borneol and (−)-borneol were 0.20 ± 0.01 and 0.16 ± 0.01 mM, respectively, and the
k
cat
values for (+)-borneol and (−)-borneol were 0.75 ± 0.01 and 0.53 ± 0.01 s
−1
, respectively. Two plant BDH genes have been reported previously. The
k
cat
and
k
cat
/

K
m

values of lavender BDH are about 1,800-fold and 500-fold lower, respectively, than those of TCU-HL1 BDH.

IMPORTANCE
The degradation of borneol in a soil microorganism through a camphor degradation pathway is reported in this study. We also report a microbial borneol dehydrogenase. The
k
cat
and
k
cat
/

K
m

values of lavender BDH are about 1,800-fold and 500-fold lower, respectively, than those of TCU-HL1 BDH. The indigenous borneol- and camphor-degrading strain isolated,
Pseudomonas
sp. strain TCU-HL1, reminds us of the time 100 years ago when Taiwan was the major producer of natural camphor in the world.
Simultaneous Transformation of Commingled Trichloroethylene, Tetrachloroethylene, and 1,4-Dioxane by a Microbially Driven Fenton Reaction in Batch Liquid Cultures
Authors: Sekar Ramanan , Taillefert Martial , DiChristina Thomas J. 
Published: August 2016

ABSTRACT

Improper disposal of 1,4-dioxane and the chlorinated organic solvents trichloroethylene (TCE) and tetrachloroethylene (also known as perchloroethylene [PCE]) has resulted in widespread contamination of soil and groundwater. In the present study, a previously designed microbially driven Fenton reaction system was reconfigured to generate hydroxyl (HO˙) radicals for simultaneous transformation of source zone levels of single, binary, and ternary mixtures of TCE, PCE, and 1,4-dioxane. The reconfigured Fenton reaction system was driven by fed batch cultures of the Fe(III)-reducing facultative anaerobe
Shewanella oneidensis
amended with lactate, Fe(III), and contaminants and exposed to alternating anaerobic and aerobic conditions. To avoid contaminant loss due to volatility, the Fe(II)-generating, hydrogen peroxide-generating, and contaminant transformation phases of the microbially driven Fenton reaction system were separated. The reconfigured Fenton reaction system transformed TCE, PCE, and 1,4-dioxane either as single contaminants or as binary and ternary mixtures. In the presence of equimolar concentrations of PCE and TCE, the ratio of the experimentally derived rates of PCE and TCE transformation was nearly identical to the ratio of the corresponding HO˙ radical reaction rate constants. The reconfigured Fenton reaction system may be applied as an
ex situ
platform for simultaneous degradation of commingled TCE, PCE, and 1,4-dioxane and provides valuable information for future development of
in situ
remediation technologies.

IMPORTANCE
A microbially driven Fenton reaction system [driven by the Fe(III)-reducing facultative anaerobe
S. oneidensis
] was reconfigured to transform source zone levels of TCE, PCE, and 1,4-dioxane as single contaminants or as binary and ternary mixtures. The microbially driven Fenton reaction may thus be applied as an
ex situ
platform for simultaneous degradation of at least three (and potentially more) commingled contaminants. Additional targets for
ex situ
and
in situ
degradation by the microbially driven Fenton reaction developed in the present study include multiple combinations of environmental contaminants susceptible to attack by Fenton reaction-generated HO˙ radicals, including commingled plumes of 1,4-dioxane, pentachlorophenol (PCP), PCE, TCE, 1,1,2-trichloroethane (TCA), and perfluoroalkylated substances (PFAS).
Metformin and other glucose-lowering drug initiation and rates of community-based antibiotic use and hospital-treated infections in patients with type 2 diabetes: a Danish nationwide population-based cohort study
Authors: Mor Anil , Petersen Irene , Sørensen Henrik T , Thomsen Reimar W 
Published: August 2016

ObjectiveData on early risk of infection in patients receiving their first treatment for type 2 diabetes are limited. We examined rates of community-based antibiotic use and hospital-treated infection in initiators of metformin and other glucose-lowering drugs (GLDs).DesignPopulation-based cohort study using medical databases.SettingGeneral practice and hospitals in Denmark.Participants131 949 patients with type 2 diabetes who initiated pharmacotherapy with a GLD between 2005 and 2012.ExposureInitial GLD used for pharmacotherapy.Main outcome measuresWe computed rates and adjusted HRs of community-based antibiotic use and hospital-treated infection associated with choice of initial GLD with reference to metformin initiation, using an intention-to-treat approach.ResultsThe rate of community-based antibiotic use was 362 per 1000 patient-years at risk (PYAR) and that for hospital-treated infection was 51 per 1000 PYAR. Compared with metformin, the risk of hospital-treated infection was slightly higher in sulfonylurea initiators (HR 1.12, 95% CI 1.08 to 1.16) and substantially higher in insulin initiators (HR 1.63, 95% CI 1.54 to 1.72) initiators after adjustment for comorbid conditions, comedications and other confounding factors. In contrast, virtually no difference was observed for overall community-based antibiotic use (HR 1.02, 95% CI 1.01 to 1.04, for sulfonylurea initiators; and 1.04, 95% CI 1.01 to 1.07, for insulin initiators).ConclusionsRates of community-based antibiotic treatment and hospitalisation for infection were high in patients receiving their first treatment for type 2 diabetes and differed with the choice of initial GLD used for pharmacotherapy.
Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) trial: the protocol for a large pilot study
Authors: Abdelaziz Tarek Samy , Lindenmeyer Antje , Baharani Jyoti , Mistry Hema , Sitch Alice , Temple R Mark , Perkins Gavin , Thomas Mark 
Published: August 2016

IntroductionAcute kidney injury (AKI) contributes to morbidity and mortality, and its care is often suboptimal and/or delayed. The Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) study is a large pilot testing provision of early specialist advice, to improve outcomes for patients with AKI.Methods and analysisThis before and after study will test an Outreach service for adult patients with AKI, identified using the national algorithm. During the 2-month before phase, AKI outcomes (30-day mortality, need for dialysis or AKI stage deterioration) will be observed in the intervention and control hospitals and their respective community areas; no interventions will be delivered. Patients will receive good standard care. During the 5-month after phase, the intervention will be delivered to patients with AKI in the intervention hospital and its area. Patients with AKI in the control hospital and its area will continue to have good standard care only. Patients already on dialysis and at end of life will be excluded. The interventions will be initially delivered via a phone call, with or without a visit to the primary clinician, aiming at rapidly establishing the aetiology, correcting reversible causes and conducting further appropriate investigation. Surviving stage 3 patients will be followed-up in an AKI clinic. We will conduct qualitative research using focus group-based discussions with primary and secondary care clinicians during the early and late phases of the trial. This will help break down potential barriers and improve care delivery.Ethics and disseminationPatients will be contacted about the study allowing them to ‘opt out’. The work of an Outreach team, guided by AKI alerts and delivering timely advice to clinicians, may improve outcomes. If the results suggest that benefits are delivered by an AKI Outreach team, this study will lead to a full cluster randomised trial.Trial registration numberNCT02398682: Pre-results.
EGFRmutation detection on lung cancer cytological specimens by the novel fully automated PCR-based IdyllaEGFRMutation Assay
Authors: De Luca Caterina , Gragnano Gianluca , Pisapia Pasquale , Vigliar Elena , Malapelle Umberto , Bellevicine Claudio , Troncone Giancarlo 
Published: August 2016

AimsIn everyday practice, epidermal growth factor receptor (EGFR) testing is centralised in referral laboratories that receive paucicellular cytological specimens. Ideally,EGFRtesting should be carried out in the centre where the patient is diagnosed such that the most cellular slide can be selected from in-house collected cytological material. However, available techniques are little standardised and difficult to be implemented in settings with little expertise in molecular testing. The IdyllaEGFRprototype assay is a rapid and fully automated test which may easily be adopted by a wider number of pathological centres. This study assessed whether an IdyllaEGFRprototype assay can be reliably applied to cytological lung cancer specimens.MethodsThe limit of detection (LOD) of the IdyllaEGFRprototype assay was assessed by cell line dilution studies. A total of 10 ng was directly placed inside an IdyllaEGFRprototype assay cartridge. Idylla results were compared with fragment length (exon 19 del) and Taqman assays.ResultsThe IdyllaEGFRprototype assay showed an LOD of 1% mutant allele and yielded valid results in 74/76 (97.3%) samples, detecting all the mutant cases (n=32) identified by standard techniques; in addition, Idylla detected two low abundanceEGFRexon 19 deletions and two G719X exon 18 point mutations, not covered by our standard reference method.ConclusionsIdyllaEGFRprototype assay is sensitive on extracted DNA and can reliably be applied on cytological samples, enabling implementation ofEGFRtesting even in less experienced diagnostic units.
Canadian Registry of LVIS Jr for Treatment of Intracranial Aneurysms (CaRLA)
Authors: Shankar Jai Jai Shiva , Quateen Aiman , Weill Alain , Tampieri Donatella , Del Pilar Cortes Maria , Fahed Robert , Patro Satya , Kaderali Zul , Lum Cheemun , Lesiuk Howard , Ahmed Uzair , Peeling Lissa , Kelly Michael E , Iancu Daniela 
Published: August 2016

IntroductionStents reduce the rate of angiographic recurrence of intracranial aneurysms. The newest stent for intracranial use is the Low-profile Visible Intraluminal Support device (LVIS Jr).ObjectiveTo assess the efficacy of the new stent in a multicenter retrospective registry.Materials and methodCenters across Canada using LVIS Jr were contacted and asked to participate in a retrospective registry of consecutive patients treated with LVIS Jr for intracranial aneurysms between January 2013 and July 2015.ResultsA total of 102 patients, with saccular aneurysms in 100 patients (72 women; age range 21–78 years; mean 56.0 years; median 57.5 years) were treated with a LVIS Jr stent. The mean maximum diameter of the dome and neck of the aneurysm and dome to neck ratios were 8.3 mm±7.7 mm, 4.4 mm±1.9 mm, and 1.86±1.22, respectively. Angiographic complications arose in 23 patients, clinical complications in 9 patients, and only 3% of permanent neurological deficits occurred. Death occurred in 1 patient, unrelated to the stent. The ruptured status of the aneurysms (OR=3.29; p=0.046) and use of LVIS Jr for bailout (OR=2.54; p=0.053) showed a trend towards significant association with higher angiographic complications. At the last available follow-up, 68 class I, 20 class II, and 12 class III results were seen.ConclusionsThe LVIS Jr stent is a safe and effective device for stent-assisted coiling, with 3% permanent neurological complications. Stent-assisted coiling continues to be technically challenging in cases of ruptured aneurysms and bailout situations.
An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer
Authors: Jin Cheng S. , Wada Hironobu , Anayama Takashi , McVeigh Patrick Z. , Hu Hsin Pei , Hirohashi Kentaro , Nakajima Takahiro , Kato Tatsuya , Keshavjee Shaf , Hwang David , Wilson Brian C. , Zheng Gang , Yasufuku Kazuhiro 
Published: August 2016

Abstract
Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current nonsurgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460, and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon nonsurgical treatment of early-stage peripheral lung cancer. Cancer Res; 76(19); 5870–80. ©2016 AACR.
Preclinical Efficacy of the Auristatin-Based Antibody–Drug Conjugate BAY 1187982 for the Treatment of FGFR2-Positive Solid Tumors
Authors: Sommer Anette , Kopitz Charlotte , Schatz Christoph A. , Nising Carl F. , Mahlert Christoph , Lerchen Hans-Georg , Stelte-Ludwig Beatrix , Hammer Stefanie , Greven Simone , Schuhmacher Joachim , Braun Manuela , Zierz Ruprecht , Wittemer-Rump Sabine , Harrenga Axel , Dittmer Frank , Reetz Frank , Apeler Heiner , Jautelat Rolf , Huynh Hung , Ziegelbauer Karl , Kreft Bertolt 
Published: August 2016

Abstract
The fibroblast growth factor receptor FGFR2 is overexpressed in a variety of solid tumors, including breast, gastric, and ovarian tumors, where it offers a potential therapeutic target. In this study, we present evidence of the preclinical efficacy of BAY 1187982, a novel antibody–drug conjugate (ADC). It consists of a fully human FGFR2 monoclonal antibody (mAb BAY 1179470), which binds to the FGFR2 isoforms FGFR2-IIIb and FGFR2-IIIc, conjugated through a noncleavable linker to a novel derivative of the microtubule-disrupting cytotoxic drug auristatin (FGFR2-ADC). In FGFR2-expressing cancer cell lines, this FGFR2-ADC exhibited potency in the low nanomolar to subnanomolar range and was more than 100-fold selective against FGFR2-negative cell lines. High expression levels of FGFR2 in cells correlated with efficient internalization, efficacy, and cytotoxic effects in vitro. Pharmacokinetic analyses in mice bearing FGFR2-positive NCI-H716 tumors indicated that the toxophore metabolite of FGFR2-ADC was enriched more than 30-fold in tumors compared with healthy tissues. Efficacy studies demonstrated that FGFR2-ADC treatment leads to a significant tumor growth inhibition or tumor regression of cell line–based or patient-derived xenograft models of human gastric or breast cancer. Furthermore, FGFR2 amplification or mRNA overexpression predicted high efficacy in both of these types of in vivo model systems. Taken together, our results strongly support the clinical evaluation of BAY 1187982 in cancer patients and a phase I study (NCT02368951) has been initiated. Cancer Res; 76(21); 6331–9. ©2016 AACR.
Association between Vitamin D Deficiency and Antinuclear Antibodies in Middle-Aged and Older U.S. Adults
Authors: Meier Helen C.S. , Sandler Dale P. , Simonsick Eleanor M. , Parks Christine G. 
Published: August 2016

Abstract
Background: Vitamin D deficiency is associated with cancer and autoimmune diseases, but little is known about the association between vitamin D and antinuclear antibodies (ANA), a biomarker of immune dysfunction in healthy populations. The objective of this study was to determine whether vitamin D deficiency is associated with ANA in middle-aged and older U.S. adults.
Methods: A cross-sectional analysis using the National Health and Nutrition Examination Survey (NHANES) 2001–2004 was conducted. Data were available for 1,012 adults aged 50 years and older. Serum 25-hydroxyvitamin D levels were measured by radioimmunoassay. ANA was measured in a 1:80 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4+).
Results: Greater vitamin D deficiency was associated with higher ANA prevalence in the unadjusted (Ptrend = 0.0002) logistic regression model and after adjustment for sex, age, education, race/ethnicity, season, and NHANES cycle (Ptrend = 0.04). After adjustment, those with severe vitamin D deficiency (&lt;10 ng/mL) had 2.99 (95% CI, 1.25–7.15) times the odds of ANA compared with having normal vitamin D levels (≥30 ng/mL), while deficient and insufficient individuals had twice the odds of ANA.
Conclusions: Among U.S. residents ages 50 and older, vitamin D deficiency was associated with higher prevalence of ANA. Vitamin D sufficiency may be important for preventing immune dysfunction in older populations.
Impact: Our findings support the growing evidence that vitamin D is an important immune modulator. Vitamin D deficiency in older adults may increase vulnerability to cancer by contributing to immune dysfunction. Cancer Epidemiol Biomarkers Prev; 25(12); 1559–63. ©2016 AACR.