bluuebunny/crossref_metadata_2025_split huggingface dataset:
To be or not to be a valid genus: the systematic position of Ophyra R.‐D. revised (Diptera: Muscidae)
Authors: GRZYWACZ ANDRZEJ , WALLMAN JAMES F. , PIWCZYŃSKI MARCIN 
Published: May 2017

AbstractOphyra Robineau‐Desvoidy is one of the better‐studied genera of the family Muscidae (Diptera). The larvae of species of this genus feed on highly decomposed organic matter of various origins, and may reveal predatory behaviour as they mature. These feeding habits, combined with the widespread distribution and close association with human dwellings of some species, give the genus commercial and medico‐legal importance. However, the systematic position of Ophyra has been a matter of debate for many years. Ophyra has been considered by muscid workers to be either a valid genus or a junior synonym of Hydrotaea Robineau‐Desvoidy. A lack of agreement about the systematic position of Ophyra has led to serious errors, particularly in the applied literature. Recent molecular and morphological studies provided contradictory information on the validity of the genus and its subfamilial classification. We revise the systematic position of Ophyra herein by means of molecular phylogenetic reconstruction. Our results are incongruent with opinions on the systematic position of Ophyra based on previously published molecular phylogenies, although they correspond with the concept of the genus based on adult morphology. All analyses of the concatenated dataset revealed Ophyra as monophyletic and placed within a paraphyletic Azeliini. Depending on the phylogenetic approach, Ophyra was placed within either a monophyletic, paraphyletic or polyphyletic Hydrotaea, yet always closely related to a certain group of species. We conclude that Ophyra, as currently defined, should not be considered a valid name, yet a detailed reconstruction of the genus Hydrotaea awaits future studies with greater increases in both taxon sampling and the number of molecular markers.
Exercise‐induced quadriceps muscle fatigue in men and women: effects of arterial oxygen content and respiratory muscle work
Authors: Dominelli Paolo B. , Molgat‐Seon Yannick , Griesdale Donald E. G. , Peters Carli M. , Blouin Jean‐Sébastien , Sekhon Mypinder , Dominelli Giulio S. , Henderson William R. , Foster Glen E. , Romer Lee M. , Koehle Michael S. , Sheel A. William 
Published: May 2017

Key points
High work of breathing and exercise‐induced arterial hypoxaemia (EIAH) can decrease O2 delivery and exacerbate exercise‐induced quadriceps fatigue in healthy men.
Women have a higher work of breathing during exercise, dedicate a greater fraction of whole‐body towards their respiratory muscles and develop EIAH.
Despite a greater reduction in men's work of breathing, the attenuation of quadriceps fatigue was similar between the sexes.
The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue.
Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing‐related changes in quadriceps muscle fatigue.
AbstractReducing the work of breathing or eliminating exercise‐induced arterial hypoxaemia (EIAH) during exercise decreases the severity of quadriceps fatigue in men. Women have a greater work of breathing during exercise, dedicate a greater fraction of whole‐body towards their respiratory muscles, and demonstrate EIAH, suggesting women may be especially susceptible to quadriceps fatigue. Healthy subjects (8 male, 8 female) completed three constant load exercise tests over 4 days. During the first (control) test, subjects exercised at ∼85% of maximum while arterial blood gases and work of breathing were assessed. Subsequent constant load exercise tests were iso‐time and iso‐work rate, but with EIAH prevented by inspiring hyperoxic gas or work of breathing reduced via a proportional assist ventilator (PAV). Quadriceps fatigue was assessed by measuring force in response to femoral nerve stimulation. For both sexes, quadriceps force was equally reduced after the control trial (−27 ± 2% baseline) and was attenuated with hyperoxia and PAV (−18 ± 1 and −17 ± 2% baseline, P < 0.01, respectively), with no sex difference. EIAH was similar between the sexes, and regardless of sex, subjects with the lowest oxyhaemoglobin saturation during the control test had the greatest quadriceps fatigue attenuation with hyperoxia (r2 = 0.79, P < 0.0001). For the PAV trial, despite reducing the work of breathing to a greater degree in men (men: 60 ± 5, women: 75 ± 6% control, P < 0.05), the attenuation of quadriceps fatigue was similar between the sexes (36 ± 4 vs. 37 ± 7%). Owing to a greater relative of the respiratory muscles in women, less of a change in work of breathing is needed to reduce quadriceps fatigue.
Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function
Authors: Betteridge Kai B. , Arkill Kenton P. , Neal Christopher R. , Harper Steven J. , Foster Rebecca R. , Satchell Simon C. , Bates David O. , Salmon Andrew H. J. 
Published: May 2017

Key points
We have developed novel techniques for paired, direct, real‐time in vivo quantification of endothelial glycocalyx structure and associated microvessel permeability.
Commonly used imaging and analysis techniques yield measurements of endothelial glycocalyx depth that vary by over an order of magnitude within the same vessel.
The anatomical distance between maximal glycocalyx label and maximal endothelial cell plasma membrane label provides the most sensitive and reliable measure of endothelial glycocalyx depth.
Sialic acid residues of the endothelial glycocalyx regulate glycocalyx structure and microvessel permeability to both water and albumin.
AbstractThe endothelial glycocalyx forms a continuous coat over the luminal surface of all vessels, and regulates multiple vascular functions. The contribution of individual components of the endothelial glycocalyx to one critical vascular function, microvascular permeability, remains unclear. We developed novel, real‐time, paired methodologies to study the contribution of sialic acids within the endothelial glycocalyx to the structural and functional permeability properties of the same microvessel in vivo. Single perfused rat mesenteric microvessels were perfused with fluorescent endothelial cell membrane and glycocalyx labels, and imaged with confocal microscopy. A broad range of glycocalyx depth measurements (0.17–3.02 μm) were obtained with different labels, imaging techniques and analysis methods. The distance between peak cell membrane and peak glycocalyx label provided the most reliable measure of endothelial glycocalyx anatomy, correlating with paired, numerically smaller values of endothelial glycocalyx depth (0.078 ± 0.016 μm) from electron micrographs of the same portion of the same vessel. Disruption of sialic acid residues within the endothelial glycocalyx using neuraminidase perfusion decreased endothelial glycocalyx depth and increased apparent solute permeability to albumin in the same vessels in a time‐dependent manner, with changes in all three true vessel wall permeability coefficients (hydraulic conductivity, reflection coefficient and diffusive solute permeability). These novel technologies expand the range of techniques that permit direct studies of the structure of the endothelial glycocalyx and dependent microvascular functions in vivo, and demonstrate that sialic acid residues within the endothelial glycocalyx are critical regulators of microvascular permeability to both water and albumin.
Draft Genome Sequence of a Caffeine-Utilizing Bacterium,
Cupriavidus
sp. Strain D384
Authors: Watahiki Saori , Kimura Nobutada 
Published: May 2017

ABSTRACT

Cupriavidus
sp. D384 was isolated from forest soil in Japan and is known to utilize caffeine as a sole source of carbon and energy. We report here the 6,835,230-bp genome sequence for this strain, which contains 6,116 predicted coding sequences, including gene operon for alkaloid degradation.
Draft Genome Sequences of Bacillus cereus E41 and Bacillus anthracis F34 Isolated from Algerian Salt Lakes
Authors: Daas Mohamed Seghir , Rosana Albert Remus R. , Acedo Jeella Z. , Nateche Farida , Kebbouche-Gana Salima , Vederas John C. , Case Rebecca J. 
Published: May 2017

ABSTRACT

Two strains of
Bacillus
,
B. cereus
E41 and
B. anthracis
F34, were isolated from a salt lake in Aïn M’lila-Oum El Bouaghi, eastern Algeria, and Ain Baida-Ouargla, southern Algeria, respectively. Their genomes display genes for the production of several bioactive secondary metabolites, including polyhydroxyalkanoate, iron siderophores, lipopeptides, and bacteriocins.
Draft Genome Sequence of the Tacrolimus-Producing Bacterium
Streptomyces tsukubaensis
F601
Authors: Zong Gongli , Zhong Chuanqing , Fu Jiafang , Qin Ronghuo , Cao Guangxiang 
Published: May 2017

ABSTRACT

Streptomyces tsukubaensis
strain F601 was found to be a producer of the immunosuppressive drug tacrolimus. The draft genome sequence of this strain was approximately 8.52 Mbp. Genes involved in the biosynthesis of tacrolimus were identified in the genome. This draft genome sequence will provide insights into the genetic basis of tacrolimus biosynthesis and regulation.
Draft Genome Sequences of Two Streptococcus pneumoniae Serotype 19A Sequence Type 226 Clinical Isolates from Hungary, Hu17 with High-Level Beta-Lactam Resistance and Hu15 of a Penicillin-Sensitive Phenotype
Authors: Rieger Martin , Denapaite Dalia , Brückner Reinhold , Maurer Patrick , Hakenbeck Regine 
Published: May 2017

ABSTRACT

The draft genome sequences of two multiple-antibiotic-resistant
Streptococcus pneumoniae
isolates from Hungary, Hu15 and Hu17, are reported here. Strain Hu15 is penicillin susceptible, whereas Hu17 is a high-level-penicillin-resistant strain. Both isolates belong to the serotype 19A sequence type 226, a single-locus variant (in the
ddl
locus) of the Hungary
19A
-6 clone.
Influence of sex, menstrual cycle, and oral contraceptives on cerebrovascular resistance and cardiorespiratory function during Valsalva or standing
Authors: Abidi Syed , Nili Misha , Serna Stephania , Kim Simon , Hazlett Christopher , Edgell Heather 
Published: May 2017

Women experience orthostatic intolerance more than men, and they experience faintness more in the early follicular [i.e., low-hormone (LH)] than luteal [i.e., high-hormone (HH)] phase of the menstrual cycle. Men ( n = 13, 25.8 ± 1.8 yr old) and women in the LH ( days 2–5; placebo) and HH ( days 18–24; high dose) phases of the menstrual cycle with (OC; n = 14, 22.0 ± 0.8 yr old) or without (NOC; n = 12, 21.8 ± 0.5 yr old) oral contraceptive (OC) use underwent the Valsalva maneuver and a supine-sit-stand protocol. Blood pressure, normalized stroke volume [stroke volume index (SVi)], cardiac output index, heart rate, end-tidal CO2, and middle cerebral artery (MCA) blood flow velocity were measured. When subjected to the Valsalva maneuver, all women had a greater increase in diastolic and mean MCA blood flow velocity than men ( P ≤ 0.065), with no significant effect of menstrual cycle phase or OC use. When subjected to the supine-sit-stand protocol, men had lower MCA blood flow velocity ( P < 0.038) than all women, and SVi was higher in men than in the NOC group in all postures ( P < 0.011) and in the OC group in the LH phase of the menstrual cycle during standing ( P = 0.010). Only men experienced higher resistance index ( P < 0.001) and pulsatility index ( P < 0.001) with standing. The OC group had lower end-tidal CO2 ( P = 0.002) than the NOC group ( P = 0.030) and men ( P ≤ 0.067). SVi ( P = 0.004) and cardiac output index ( P = 0.008) were higher in the OC than NOC group. A tendency toward a lower mean MCA blood flow velocity ( P = 0.058) and higher SVi ( P = 0.059) and pulsatility index ( P = 0.058) was noted in the HH than LH phase. Mean arterial pressure was higher in the OC than NOC group in the LH phase ( P = 0.049) and lower in the HH than LH phase ( P = 0.014). Our results indicate that cycling estrogens/progestins can influence ventilatory, cardiovascular, and/or cerebrovascular physiology. NEW & NOTEWORTHY We have found sex differences in the cerebrovascular response to the Valsalva maneuver and standing. Men have greater cerebral vasoconstriction (or women have greater cerebral vasodilation) during late phase II of the Valsalva maneuver, and the cerebrovascular resistance index increases in men, but not in women, during standing. Furthermore, our findings indicate that both the menstrual cycle phase and oral contraceptive use can influence cardiovascular function both at rest and during active standing.
Targeting FBW7 as a Strategy to Overcome Resistance to Targeted Therapy in Non–Small Cell Lung Cancer
Authors: Ye Mingxiang , Zhang Yong , Zhang Xinxin , Zhang Jianbin , Jing Pengyu , Cao Liang , Li Nan , Li Xia , Yao Libo , Zhang Jian , Zhang Jian 
Published: May 2017

Abstract
Inhibition of EGFR and anaplastic lymphoma kinase (ALK) signaling is highly effective in a subgroup of non–small cell lung cancer (NSCLC) patients with distinct clinicopathologic features. However, resistance to EGFR and ALK inhibitors inevitably occurs, and the molecular mechanism underlying resistance is not fully understood. In this study, we report a PI3K/Akt- and MEK/ERK–independent resistance mechanism by which loss of the E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBW7α) leads to targeted therapy resistance via stabilization of antiapoptotic protein MCL-1. Using a panel of in vitro and in vivo studies, we showed that the regulatory machinery responsible for MCL-1 protein degradation was a step-wise event involving phosphorylation and nucleus translocation. ERK cooperated with GSKβ to phosphorylate MCL-1 Ser159 residue, which enabled MCL-1 to translocate into the nucleus and bind FBW7. Defects in this sequence impaired MCL-1 degradation and cell apoptosis, recapitulating phenotypes observed in FBW7 deficiency. Downregulation of FBW7 was found in EGFR inhibitor–resistant human NSCLC specimens and correlated with increased MCL-1 protein expression. Reactivation of FBW7 sensitized resistant cells to targeted therapy and facilitated MCL-1 degradation. Overall, our study provides proof-of-principle insight into a PI3K/Akt- and MEK/ERK–independent resistant model and suggests that targeting FBW7 can overcome resistance to targeted therapy. Cancer Res; 77(13); 3527–39. ©2017 AACR.
Mismatch Repair Proteins Initiate Epigenetic Alterations during Inflammation-Driven Tumorigenesis
Authors: Maiuri Ashley R. , Peng Michael , Podicheti Ram , Sriramkumar Shruthi , Kamplain Caitlin M. , Rusch Douglas B. , DeStefano Shields Christina E. , Sears Cynthia L. , O'Hagan Heather M. 
Published: May 2017

Abstract
Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model of inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment of epigenetic proteins to chromatin, initiating methylation and gene silencing in tumors. Compared with normal epithelium and noninflammation-induced tumors, inflammation-induced tumors gained DNA methylation at CpG islands, some of which are associated with putative tumor suppressor genes. Hypermethylated genes exhibited enrichment of repressive chromatin marks and reduced expression prior to tumorigenesis, at a time point coinciding with peak levels of inflammation-associated DNA damage. Loss of MutS homolog 2 (MSH2), a mismatch repair (MMR) protein, abrogated early inflammation-induced epigenetic alterations and DNA hypermethylation alterations observed in inflammation-induced tumors. These results indicate that early epigenetic alterations initiated by inflammation and MMR proteins lead to gene silencing during tumorigenesis, revealing a novel mechanism of epigenetic alterations in inflammation-driven cancer. Understanding such mechanisms will inform development of pharmacotherapies to reduce carcinogenesis. Cancer Res; 77(13); 3467–78. ©2017 AACR.
SMAD4 Loss Is Associated with Cetuximab Resistance and Induction of MAPK/JNK Activation in Head and Neck Cancer Cells
Authors: Ozawa Hiroyuki , Ranaweera Ruchira S. , Izumchenko Evgeny , Makarev Eugene , Zhavoronkov Alex , Fertig Elana J. , Howard Jason D. , Markovic Ana , Bedi Atul , Ravi Rajani , Perez Jimena , Le Quynh-Thu , Kong Christina S. , Jordan Richard C. , Wang Hao , Kang Hyunseok , Quon Harry , Sidransky David , Chung Christine H. 
Published: May 2017

Abstract
Purpose: We previously demonstrated an association between decreased SMAD4 expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC.
Experimental Design: SMAD4 expression was assessed by IHC in 130 newly diagnosed and 43 patients with recurrent HNSCC. Correlative statistical analysis with clinicopathologic data was also performed. OncoFinder, a bioinformatics tool, was used to analyze molecular signaling in TCGA tumors with low or high SMAD4 mRNA levels. The role of SMAD4 was investigated by shRNA knockdown and gene reconstitution of HPV-negative HNSCC cell lines in vitro and in vivo.
Results: Our analysis revealed that SMAD4 loss was associated with an aggressive, HPV-negative, cetuximab-resistant phenotype. We found a signature of prosurvival and antiapoptotic pathways that were commonly dysregulated in SMAD4-low cases derived from TCGA-HNSCC dataset and an independent oral cavity squamous cell carcinoma (OSCC) cohort obtained from GEO. We show that SMAD4 depletion in an HNSCC cell line induces cetuximab resistance and results in worse survival in an orthotopic mouse model in vivo. We implicate JNK and MAPK activation as mediators of cetuximab resistance and provide the foundation for the concomitant EGFR and JNK/MAPK inhibition as a potential strategy for overcoming cetuximab resistance in HNSCCs with SMAD4 loss.
Conclusions: Our study demonstrates that loss of SMAD4 expression is a signature characterizing the cetuximab-resistant phenotype and suggests that SMAD4 expression may be a determinant of sensitivity/resistance to EGFR/MAPK or EGFR/JNK inhibition in HPV-negative HNSCC tumors. Clin Cancer Res; 23(17); 5162–75. ©2017 AACR.
Antitumor Synergism and Enhanced Survival with a Tumor Vasculature–Targeted Enzyme Prodrug System, Rapamycin, and Cyclophosphamide
Authors: Krais John J. , Virani Needa , McKernan Patrick H. , Nguyen Quang , Fung Kar-Ming , Sikavitsas Vassilios I. , Kurkjian Carla , Harrison Roger G. 
Published: May 2017

Abstract
Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with Annexin A1 or Annexin A5. Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart nonnative methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of nontoxic selenomethionine. The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of nonnative proteins and/or DNA required with other enzyme prodrug systems. The enzyme fusion exhibits strong and stable in vitro binding with dissociation constants in the nanomolar range for both human and mouse breast cancer cells and in a cell model of tumor vascular endothelium. Daily administration of the therapy suppressed growth of highly aggressive triple-negative murine 4T1 mammary tumors in immunocompetent BALB/cJ mice and MDA-MB-231 tumors in SCID mice. Treatment did not result in the occurrence of negative side effects or the elicitation of neutralizing antibodies. On the basis of the vasculature-targeted nature of the therapy, combinations with rapamycin and cyclophosphamide were evaluated. Rapamycin, an mTOR inhibitor, reduces the prosurvival signaling of cells in a hypoxic environment potentially exacerbated by a vasculature-targeted therapy. IHC revealed, unsurprisingly, a significant hypoxic response (increase in hypoxia-inducible factor 1 α subunit, HIF1A) in the enzyme prodrug–treated tumors and a dramatic reduction of HIF1A upon rapamycin treatment. Cyclophosphamide, an immunomodulator at low doses, was combined with the enzyme prodrug therapy and rapamycin; this combination synergistically reduced tumor volumes, inhibited metastatic progression, and enhanced survival. Mol Cancer Ther; 16(9); 1855–65. ©2017 AACR.
Synergistic Effect of Dofetilide and Mexiletine on Prevention of Atrial Fibrillation
Authors: Liu Guizhi , Xue Xiaolin , Gao Chuanyu , Huang Jiaqi , Qi Datun , Zhang Yanzhou , Dong Jian‐Zeng , Ma Chang‐Sheng , Yan Gan‐Xin 
Published: May 2017

Background

Although atrial fibrillation (
AF
) is the most common abnormal heart rhythm and its prevalence continues to rise, there is a marked paucity of effective and safe antiarrhythmic drugs for
AF
. This study was done to test whether combined use of dofetilide and mexiletine exhibits not only a synergistic effect on
AF
suppression but also a safer profile in drug‐induced ventricular proarrhythmias.

Methods and Results

The effects of dofetilide plus mexiletine on atrial effective refractory period (
ERP
),
AF
inducibility,
QT
, and
QT
‐related ventricular arrhythmias were studied using the isolated arterially perfused rabbit atrial and ventricular wedge preparations. Dofetilide or mexiletine alone mildly to moderately prolonged atrial
ERP
, but their combined use produced a markedly rate‐dependent increase in atrial
ERP
. Dofetilide (3 nmol/L) plus mexiletine (10 μmol/L) increased the
ERP
by 28.2% from 72.2±5.7 to 92.8±5.9 ms (n=9,
P
<0.01) at a pacing rate of 0.5 Hz and by 94.5% from 91.7±5.2 to 178.3±12.0 ms (n=9,
P
<0.01) at 3.3 Hz. Dofetilide plus mexiletine strongly suppressed
AF
inducibility. On the other hand, dofetilide at 10 nmol/L produced marked
QT
and T
p‐e
prolongation, steeper
QT
‐
BCL
and T
p‐e
‐
BCL
slopes, and induced early afterdepolarizations and torsade de pointes in the ventricular wedges. Mexiletine at 10 μmol/L reduced dofetilide‐induced
QT
and T
p‐e
prolongation,
QT
‐
BCL
and T
p‐e
‐
BCL
slopes, and abolished early afterdepolarizations and torsade de pointes.

Conclusions

In rabbits, combined use of dofetilide and mexiletine not only synergistically increases atrial
ERP
and effectively suppresses
AF
inducibility, but also markedly reduces
QT
liability and torsade de pointes risk posed by dofetilide alone.
Language contact, borrowing and code switching
Authors: Alvanoudi Angeliki 
Published: May 2017

Abstract
The present study is an in-depth investigation of the Greek language spoken by immigrants in Far North Queensland, Australia. The study focuses on contact-induced changes in the language, such as borrowing of lexemes and discourse patterns, and on code switching. The data analyzed derive from participant observation and some 23 hours of audio and video-recorded conversations with first- and second-generation Greek immigrants that were collected during fieldwork in 2013 in Far North Queensland. The study contributes to the investigation of the structure and use of Greek in the diaspora by integrating perspectives from contact linguistics and interactional approaches to code switching.