bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excess Iodide Induces an Acute Inhibition of the Sodium/Iodide Symporter in Thyroid Male Rat Cells by Increasing Reactive Oxygen Species
Authors: Arriagada Alejandro A. , Albornoz Eduardo , Opazo Ma. Cecilia , Becerra Alvaro , Vidal Gonzalo , Fardella Carlos , Michea Luis , Carrasco Nancy , Simon Felipe , Elorza Alvaro A. , Bueno Susan M. , Kalergis Alexis M. , Riedel Claudia A. 
Published: January 2015

AbstractNa+/I− symporter (NIS) mediates iodide (I−) uptake in the thyroid gland, the first and rate-limiting step in the biosynthesis of the thyroid hormones. The expression and function of NIS in thyroid cells is mainly regulated by TSH and by the intracellular concentration of I−. High doses of I− for 1 or 2 days inhibit the synthesis of thyroid hormones, a process known as the Wolff-Chaikoff effect. The cellular mechanisms responsible for this physiological response are mediated in part by the inhibition of I− uptake through a reduction of NIS expression. Here we show that inhibition of I− uptake occurs as early as 2 hours or 5 hours after exposure to excess I− in FRTL-5 cells and the rat thyroid gland, respectively. Inhibition of I− uptake was not due to reduced NIS expression or altered localization in thyroid cells. We observed that incubation of FRTL-5 cells with excess I− for 2 hours increased H2O2 generation. Furthermore, the inhibitory effect of excess I− on NIS-mediated I− transport could be recapitulated by H2O2 and reverted by reactive derived oxygen species scavengers. The data shown here support the notion that excess I− inhibits NIS at the cell surface at early times by means of a posttranslational mechanism that involves reactive derived oxygen species.
γ-Oryzanol Protects Pancreatic β-Cells Against Endoplasmic Reticulum Stress in Male Mice
Authors: Kozuka Chisayo , Sunagawa Sumito , Ueda Rei , Higa Moritake , Tanaka Hideaki , Shimizu-Okabe Chigusa , Ishiuchi Shogo , Takayama Chitoshi , Matsushita Masayuki , Tsutsui Masato , Miyazaki Jun-ichi , Oyadomari Seiichi , Shimabukuro Michio , Masuzaki Hiroaki 
Published: January 2015

Abstract
Endoplasmic reticulum (ER) stress is profoundly involved in dysfunction of β-cells under high-fat diet and hyperglycemia. Our recent study in mice showed that γ-oryzanol, a unique component of brown rice, acts as a chemical chaperone in the hypothalamus and improves feeding behavior and diet-induced dysmetabolism. However, the entire mechanism whereby γ-oryzanol improves glucose metabolism throughout the body still remains unclear. In this context, we tested whether γ-oryzanol reduces ER stress and improves function and survival of pancreatic β-cells using murine β-cell line MIN6. In MIN6 cells with augmented ER stress by tunicamycin, γ-oryzanol decreased exaggerated expression of ER stress-related genes and phosphorylation of eukaryotic initiation factor-2α, resulting in restoration of glucose-stimulated insulin secretion and prevention of apoptosis. In islets from high-fat diet-fed diabetic mice, oral administration of γ-oryzanol improved glucose-stimulated insulin secretion on following reduction of exaggerated ER stress and apoptosis. Furthermore, we examined the impact of γ-oryzanol on low-dose streptozotocin-induced diabetic mice, where exaggerated ER stress and resultant apoptosis in β-cells were observed. Also in this model, γ-oryzanol attenuated mRNA level of genes involved in ER stress and apoptotic signaling in islets, leading to amelioration of glucose dysmetabolism. Taken together, our findings demonstrate that γ-oryzanol directly ameliorates ER stress-induced β-cell dysfunction and subsequent apoptosis, highlighting usefulness of γ-oryzanol for the treatment of diabetes mellitus.
Bisphenol A Alters Autonomic Tone and Extracellular Matrix Structure and Induces Sex-Specific Effects on Cardiovascular Function in Male and Female CD-1 Mice
Authors: Belcher Scott M. , Gear Robin B. , Kendig Eric L. 
Published: January 2015

AbstractThe aim of this study was to determine whether bisphenol A (BPA) has adverse effects on cardiovascular functions in CD-1 mice and define sex-specific modes of BPA action in the heart. Dams and analyzed progeny were maintained on a defined diet containing BPA (0.03, 0.3, 3, 30, or 300 ppm) that resulted in BPA exposures from 4–5 to approximately 5000 μg/kg · d or a diet containing 17α-ethinyl estradiol (EE; ∼0.02, 0.2, and 0.15 μg/kg · d) as an oral bioavailable estrogen control. Assessment of electrocardiogram parameters using noninvasive methods found that ventricular functions in both male and female mice were not altered by either BPA or EE. However, exposure-related changes in the rates of ventricular contraction, suggestive of a shift in sympathovagal balance of heart rate control toward increased parasympathetic activity, were detected in males. Decreased systolic blood pressure was observed in males exposed to BPA above 5 μg/kg · d and in females from the highest BPA exposure group. Morphometric histological measures revealed sexually dimorphic changes in the composition of the cardiac collagen extracellular matrix, increases in fibrosis, and evidence of modest exposure-related remodeling. Experiments using the α-selective adrenergic agonist phenylephrine found that BPA enhanced reflex bradycardia in females, but not males, revealed that BPA and EE exposure sex specifically altered the sympathetic regulation of the baroreflex circuits. Increased sensitivity to the cardiotoxic effects of the β-adrenergic agonist isoproterenol was observed in BPA- and EE-exposed females. This effect was not observed in males, in which BPA or EE exposures were protective of isoproterenol-induced ischemic damage and hypertrophy. The results of RNA sequence analysis identified significant sex-specific changes in gene expression in response to BPA that were consistent with the observed exposure-related phenotypic changes in the collagenous and noncollagenous extracellular matrix, cardiac remodeling, altered autonomic responses, changes in ion channel and transporter functions, and altered glycolytic and lipid metabolism.
PAPSS2 Deficiency Causes Androgen Excess via Impaired DHEA Sulfation—In Vitro and in Vivo Studies in a Family Harboring Two Novel PAPSS2 Mutations
Authors: Oostdijk Wilma , Idkowiak Jan , Mueller Jonathan W. , House Philip J. , Taylor Angela E. , O'Reilly Michael W. , Hughes Beverly A. , de Vries Martine C. , Kant Sarina G. , Santen Gijs W. E. , Verkerk Annemieke J. M. H. , Uitterlinden André G. , Wit Jan M. , Losekoot Monique , Arlt Wiebke 
Published: January 2015

Context:
PAPSS2 (PAPS synthase 2) provides the universal sulfate donor PAPS (3′-phospho-adenosine-5′-phosphosulfate) to all human sulfotransferases, including SULT2A1, responsible for sulfation of the crucial androgen precursor dehydroepiandrosterone (DHEA). Impaired DHEA sulfation is thought to increase the conversion of DHEA toward active androgens, a proposition supported by the previous report of a girl with inactivating PAPSS2 mutations who presented with low serum DHEA sulfate and androgen excess, clinically manifesting with premature pubarche and early-onset polycystic ovary syndrome.

Patients and Methods:
We investigated a family harboring two novel PAPSS2 mutations, including two compound heterozygous brothers presenting with disproportionate short stature, low serum DHEA sulfate, but normal serum androgens. Patients and parents underwent a DHEA challenge test comprising frequent blood sampling and urine collection before and after 100 mg DHEA orally, with subsequent analysis of DHEA sulfation and androgen metabolism by mass spectrometry. The functional impact of the mutations was investigated in silico and in vitro.

Results:
We identified a novel PAPSS2 frameshift mutation, c.1371del, p.W462Cfs*3, resulting in complete disruption, and a novel missense mutation, c.809G&gt;A, p.G270D, causing partial disruption of DHEA sulfation. Both patients and their mother, who was heterozygous for p.W462Cfs*3, showed increased 5α-reductase activity at baseline and significantly increased production of active androgens after DHEA intake. The mother had a history of oligomenorrhea and chronic anovulation that required clomiphene for ovulation induction.

Conclusions:
We provide direct in vivo evidence for the significant functional impact of mutant PAPSS2 on DHEA sulfation and androgen activation. Heterozygosity for PAPSS2 mutations can be associated with a phenotype resembling polycystic ovary syndrome.
Ketamine infusion for patients receiving extracorporeal membrane oxygenation support: a case series
Authors: Tellor Bethany , Shin Nicole , Graetz Thomas J. , Avidan Michael S. 
Published: January 2015

The use of ketamine infusion for sedation/analgesia in patients receiving extracorporeal membrane oxygenation (ECMO) therapy has not been described. The aims of this retrospective cohort study were to explore whether ketamine infusion for patients requiring ECMO therapy was associated with altered RASS scores, decreased concurrent sedative or opioid use, or with changes in vasopressor requirements. All patients on ECMO who received ketamine infusions in addition to sedative and/or opioid infusions between December 2013 and October 2014 at Barnes-Jewish Hospital in St. Louis were retrospectively identified. Patient characteristics and process of care data were collected.A total of 26 ECMO patients receiving ketamine infusion were identified. The median (inter quartile range [range]) age was 40 years (30-52 [25-66]) with 62% male. The median starting infusion rate of ketamine was 50 mg/hr (30-50 [6-150]) and it was continued for a median duration of 9 days (4-14 [0.2-21]). Prior to ketamine, 14/26 patients were receiving vasopressor infusions to maintain hemodynamic stability. Ketamine initiation was associated with a decrease in vasopressor requirement in 11/26 patients within two hours, and 0/26 required an increase (p<0.001). All patients were receiving sedative and/or opioid infusions at the time of ketamine initiation; 9/26 had a decrease in these infusions within two hours of ketamine initiation, and 1/26 had an increase (p=0.02; odds ratio for decrease to increase = 9; 95% CI, 1.14 to 71.04). The median (IQR[range]) RASS score 24 hours before ketamine initiation was -4 (-3 to -5, [0 to -5]) and after ketamine was -4 (-3 to -4 [-1 to -5]) (P= 0.614).Ketamine infusion can be used as an adjunctive sedative agent in patients receiving ECMO and may decrease concurrent sedative and/or opioid infusions without altering RASS scores. The hemodynamic effects of ketamine may provide the benefit of decreasing vasopressor requirements.
IMPROVEMENT OF POINT LEPREAU GENERATING STATION ROP DETECTOR CHARACTERISTICS BY ADJUSTING GAINS IN COMPENSATION AMPLIFIERS
Authors: Anghel V. , Basque M.-J. , Comeau D. , Sur B. , Taylor D. 
Published: January 2015

Canadian Pressurized Heavy Water Reactors are protected against reactor overpower by 2 independent shutdown systems: Shut Down System 1 and 2. At Point Lepreau Generating Station, these shutdown systems can be actuated by signals from Platinum-clad Inconel In-Core Flux Detectors measuring the neutron flux. These detectors have a complex dynamic behaviour, characterized by “prompt” and “delayed” components with respect to immediate changes in the in-core neutron flux. In aging detectors, it was found that the prompt response decreases. A detector response that actuates the shutdown system effectively has to have a large prompt response and a small delayed response. These required responses may be obtained by adjusting the dynamic compensation amplifiers (compensator) settings. This paper presents the measured results of a compensation adjustment procedure for the in-core platinum-clad Inconel detectors. The compensation is computed from the detector parameters estimated by VS, a fully automated and qualified computer program that analyzes the response of the detectors.
Bone Marrow Necrosis
Authors: Wool Geoffrey D. , Deucher Anne 
Published: January 2015

Abstract

Objectives:
Bone marrow can undergo necrosis for many different causes; malignant causes are reported to be more frequent.

Methods:
We undertook a 10-year retrospective review of all bone marrow biopsy specimens with bone marrow necrosis at our institution.

Results:
Identified cases represented approximately 0.3% of our bone marrow cases. Most identified bone marrow cases with necrosis were involved by metastatic tumor or hematolymphoid malignancy (90% of total) in relatively equal proportions. In those cases of bone marrow necrosis with hematolymphoid malignancy, lymphoid disease predominated and the necrosis was often seen in the setting of chemotherapy. In metastatic tumor cases, necrosis seemed to enrich in prostate adenocarcinoma and Ewing sarcoma/primitive neuroectodermal tumor; neuroblastoma showed much less necrosis. Ten percent of patients with bone marrow necrosis had no underlying malignancy, and the associated causes varied.

Conclusions:
The causes of bone marrow necrosis are diverse but should always prompt careful assessment for malignancy and infectious etiology.
The Vascular Marker CD31 Also Highlights Histiocytes and Histiocyte-Like Cells Within Cutaneous Tumors
Authors: Vanchinathan Vijay , Mizramani Neda , Kantipudi Ramya , Schwartz Erich J. , Sundram Uma N. 
Published: January 2015

Abstract

Objectives:
While useful in diagnosing angiosarcomas, CD31 can also highlight histiocytes within soft tissue tumors and lead to errors in diagnosis. We sought to determine how often CD31 highlights cutaneous histiocytomas and histiocytoma mimics.

Methods:
We examined eight epithelioid cell histiocytomas (ECHs), 12 xanthogranulomas (XGs), nine cases of Langerhans cell histiocytosis (LCH), eight reticulohistiocytomas, 11 xanthomas, 29 atypical fibroxanthomas, nine granular cell tumors, four cases of angiolymphoid hyperplasia with eosinophilia, nine intradermal Spitz nevi, and nine angiosarcomas with antibodies directed against CD31, CD34, CD163, and factor VIII.

Results:
CD31 marked cells in three of 12 XGs, four of nine cases of LCH, one of eight reticulohistiocytomas, one of 11 xanthomas, 10 of 29 atypical fibroxanthomas, four of four cases of angiolymphoid hyperplasia with eosinophilia, nine of nine angiosarcomas, zero of nine granular cell tumors, and zero of eight ECHs. CD34 and factor VIII were negative in all nonvascular cases.

Conclusions:
Our results indicate that CD31 can mark lesional cells and imitate vascular tumors in cutaneous histiocytomas and histiocytoma mimics, an error that can be avoided by using a panel of antibodies.
Enhanced FHL2 and TGF-β1 Expression Is Associated With Invasive Growth and Poor Survival in Malignant Melanomas
Authors: Westphal Philipp , Mauch Cornelia , Florin Alexandra , Czerwitzki Jacqueline , Olligschläger Nina , Wodtke Claudia , Schüle Roland , Büttner Reinhard , Friedrichs Nicolaus 
Published: January 2015

Abstract

Objectives:
This study examines the expression and the role of four-and-a-half LIM domains protein 2 (FHL2) and transforming growth factor β1 (TGF-β1) in human malignant melanoma. It is determined whether both proteins influence melanoma survival time.

Methods:
We analyzed the immunohistochemical staining intensities of FHL2 and TGF-β1 in normal skin and in 50 malignant melanomas with different mutation status (BRAF-V600E, NRAS codon 61 mutation, and wild type). Survival data were available for 45 cases.

Results:
In melanocytes of nonneoplastic human skin, FHL2 expression was absent. In contrast, 38 (76%) of 50 melanomas showed strong cytoplasmic and partly nuclear FHL2 expression. At the invasion front, cytoplasmic TGF-β1 staining was observed in 32 (64%) of 50 melanomas, and a correlation of FHL2 and TGF-β1 staining intensities was detectable. In follow-up analyses, enhanced FHL2 and TGF-β1 staining intensities in the tumor invasion front were associated with poor survival.

Conclusions:
Enhanced FHL2 and TGF-β1 expression is correlated with poor survival in human malignant melanoma. Protumorigenic effects of autocrine TGF-β1 secretion might be exerted by induction of FHL2 expression in melanoma cells. Since melanomas treated with targeted therapies often do not show sufficient response rates, inhibition of FHL2 and/or TGF-β1 might be a promising therapeutic approach.
Detection of Acetylcholine Receptor Modulating Antibodies by Flow Cytometry
Authors: Lozier Bucky K. , Haven Thomas R. , Astill Mark E. , Hill Harry R. 
Published: January 2015

Abstract

Objectives:
To determine the clinical utility and performance characteristics of a laboratory-adapted flow cytometric method for the detection of acetylcholine receptor (AChR) modulating antibodies in myasthenia gravis (MG).

Methods:
Serum samples from 120 healthy donors and 100 patients with suspected MG were assessed for the ability to reduce surface AChR concentrations (antigenic modulation) in RD (TE671) or DB40 human muscle cell lines by flow cytometry. Reference ranges were established by receiver operating characteristic curve analysis, and results were then compared with those of the current radioimmunoassay (RIA).

Results:
Flow cytometric results from the RD cell line had an interpretive threshold of 46% modulation or greater and correlated best (98% sensitivity, 99% specificity) with those of the current RIA.

Conclusions:
The new flow cytometric method using the RD cell platform provided higher quality clinical results, a more robust and efficient assay format, a significant cost savings, and less environmental burden.
Fabrication and characterization of nanostructured
thermoelectric FexCo1-xSb3
Authors: Tafti Mohsen Yakshi , Saleemi Mohsin , Toprak Muhammet S. , Johnsson Mats , Jacquot Alexandre , Jägle Martin , Muhammed Mamoun 
Published: January 2015

Abstract
A novel synthesis route for the fabrication
of p-type nanostructured skutterudite, FexCo1-xSb3
in large quantity is reported. This scalable synthesis route
provides nano-engineered material with less impact on
the environment compared to conventional synthesis
procedures. Several Fe substituted compositions have
been synthesized to confirm the feasibility of the process.
The process consists of a nano-sized precursor fabrication
of iron and cobalt oxalate, and antimony oxides
by chemical co-precipitation. Further thermochemical
processes result in the formation of iron substituted
skutterudites. The nanopowders are compacted by Spark
Plasma Sintering (SPS) technique in order to maintain
nanostructure. Detailed physicochemical as well as
thermoelectric transport properties are evaluated. Results
reveal strongly reduced thermal conductivity values
compared to conventionally prepared counterparts, due
to nanostructuring. P-type characteristic was observed
from the Seebeck measurements while electrical
conductivity is high and shows metallic behavior.
The highest TE figure of merit of 0.25 at 800 K has been
achieved, which is strongly enhanced with respect to the
mother compound CoSb3. This suggests the promise of
the utilized method of fabrication and processing for TE
applications with improved performance.
Generation of High Frequency Pin-hole Discharge
in Water Solutions
Authors: Krčma František , Kozáková Zdenka , Vašíček Michal 
Published: January 2015

Abstract
This paper presents results on electric discharge
generation by high frequency high voltage (15–100 kHz)
in NaCl solutions with different initial conductivity
(100–1300 mS cm-1), and compares them with DC discharge
in the same electrode configuration. A batch plasma reactor
in the pin-hole configuration contained a ceramic dielectric
barrier separating two planar stainless steel electrodes;
barrier thickness of 0.6 mm and pin-hole diameter of
0.6 mm was used. Lissajous charts were evaluated from
electric measurements for different discharge phases
(electrolysis, bubble formation and discharge regular
operation). Breakdown moments for different solution
conductivities were determined from discharge power
evaluation as a function of applied frequency. Breakdown
voltage amplitude was decreased by the increasing
conductivity in both regimes while frequency and current
decreased. Changes of physical parameters (temperature,
solution conductivity and pH) as well as production of
hydrogen peroxide at different solution conductivities were
compared. Solution conductivity was increased in both
discharge regimes and with the initial conductivity value.
Solution temperature was increased by the discharge in
both regimes and with the increasing initial conductivity,
too. Solution pH dropped to acidic conditions when HF or
DC positive regime was applied while it was enhanced by
DC negative regime.
Glycoprofiling of cancer biomarkers: Label-free
electrochemical lectin-based biosensors
Authors: Pihíková Dominika , Kasák Peter , Tkac Jan 
Published: January 2015

Abstract
Glycosylation of biomolecules is one of the
most prevalent post- and co-translational modification in
a human body, with more than half of all human proteins
being glycosylated. Malignant transformation of cells
influences glycosylation machinery resulting in subtle
changes of the glycosylation pattern within the cell
populations as a result of cancer. Thus, an altered terminal
glycan motif on glycoproteins could provide a warning
signal about disease development and progression
and could be applied as a reliable biomarker in cancer
diagnostics. Among all highly effective glycoprofiling
tools, label-free electrochemical impedance spectroscopy
(EIS)-based biosensors have emerged as especially
suitable tool for point-of-care early-stage cancer
detection. Herein, we highlight the current challenges
in glycoprofiling of various cancer biomarkers by
ultrasensitive impedimetric-based biosensors with low
sample consumption, low cost fabrication and simple
miniaturization. Additionally, this review provides a short
introduction to the field of glycomics and lectinomics and
gives a brief overview of glycan alterations in different
types of cancer.
Unexpected formation of [M]2+ from [M+CuCl+H]2+
ions under CID conditions, where M is a molecule
of 3,5-bis(2,2’-bipyridin-4-ylethynyl)benzoic acid
or its methyl ester
Authors: Frański Rafał , Zalas Maciej , Gierczyk Błażej , Cegłowski Michał , Schroeder Grzegorz , Kozik Tomasz , Hoffmann Marcin 
Published: January 2015

Abstract
[M+CuCl+H]2+ ions were generated using
electrospray ionization (ESI); where M is a molecule
of 3,5-bis(2,2’-bipyridin-4-ylethynyl)benzoic acid or its
methyl ester (1 and 2, respectively). The ions were subjected
to CID-MS/MS analysis. It was found that their gas phase
decomposition lead to the formation of rare di-cations
[M]2+, namely [1]2+ and [2]2+ ions. The formation of [1]2+ ion
from [3+H+CuCl]2+ ion in the second fragmentation, where
3 is ethyl ester of 3,5-bis(2,2-bipyridin-4-ylethynyl)benzoic
acid, was also observed since in the first fragmentation
step the loss of ethylene molecule from [3+H+CuCl]2+ ion
took place. To the best of our knowledge, it is the first time
that [M]2+ ions formation from respective metal complexes
has been reported. It is also unusual that formation
of [M]2+ ions is not accompanied by formation of [M]+∙
ions. Furthermore, as expected, theoretical calculation
and electron ionization mass spectra show that 1 and 2 are
not especially prone to form [M]2+ ions. Thus formation of
[M]2+ ions under CID conditions is very surprising.