bluuebunny/crossref_metadata_2025_split huggingface dataset:
ERKs in Cancer: Friends or Foes?
Authors: Deschênes-Simard Xavier , Kottakis Filippos , Meloche Sylvain , Ferbeyre Gerardo 
Published: January 2014

Abstract
The extracellular signal–regulated kinase ERK1 and ERK2 (ERK1/2) cascade regulates a variety of cellular processes by phosphorylating multiple target proteins. The outcome of its activation ranges from stimulation of cell survival and proliferation to triggering tumor suppressor responses such as cell differentiation, cell senescence, and apoptosis. This pathway is intimately linked to cancer as several of its upstream activators are frequently mutated in human disease and are shown to accelerate tumorigenesis when engineered in the mouse genome. However, measurement of activated ERKs in human cancers or mouse models does not always support a role in tumorigenesis, and data consistent with a role in tumor suppression have been reported as well. The intensity of ERK signaling, negative feedback loops that regulate the pathway, and cross-talks with other signaling pathways, seem to be of primary importance in determining the final cellular outcome. Cell senescence, a putative tumor-suppression mechanism, depends on high-intensity ERK signals that trigger phosphorylation-dependent protein degradation of multiple proteins required for cell-cycle progression. This response may be circumvented during carcinogenesis by a variety of mechanisms, some of them yet to be discovered, which in essence turn ERK functions from tumor suppression to tumor promotion. The use of pharmacologic inhibitors targeting this pathway must be carefully evaluated so they are applied to cases in which ERKs are mainly oncogenic. Cancer Res; 74(2); 412–9. ©2014 AACR.
AIP1 Mediates Vascular Endothelial Cell Growth Factor Receptor-3–Dependent Angiogenic and Lymphangiogenic Responses
Authors: Zhou Huanjiao Jenny , Chen Xiaodong , Huang Qunhua , Liu Renjing , Zhang Haifeng , Wang Yingdi , Jin Yu , Liang Xiaoling , Lu Lin , Xu Zhe , Min Wang 
Published: January 2014

Objective—
To investigate the novel function of ASK1-interacting protein-1 (AIP1) in vascular endothelial cell growth factor receptor (VEGFR)-3 signaling, and VEGFR-3–dependent angiogenesis and lymphangiogenesis.

Approach and Results—

AIP1, a signaling scaffold protein, is highly expressed in the vascular endothelium. We have previously reported that AIP1 functions as an endogenous inhibitor in pathological angiogenesis by blocking VEGFR-2 activity. Surprisingly, here we observe that mice with a global deletion of AIP1-knockout mice (AIP1-KO) exhibit reduced retinal angiogenesis with less sprouting and fewer branches. Vascular endothelial cell (but not neuronal)–specific deletion of AIP1 causes similar defects in retinal angiogenesis. The reduced retinal angiogenesis correlates with reduced expression in VEGFR-3 despite increased VEGFR-2 levels in AIP1-KO retinas. Consistent with the reduced expression of VEGFR-3, AIP1-KO show delayed developmental lymphangiogenesis in neonatal skin and mesentery, and mount weaker VEGF-C–induced cornea lymphangiogenesis. In vitro, human lymphatic endothelial cells with AIP1 small interfering RNA knockdown, retinal endothelial cells, and lymphatic endothelial cells isolated from AIP1-KO all show attenuated VEGF-C–induced VEGFR-3 signaling. Mechanistically, we demonstrate that AIP1 via
vegfr-3
–specific
miR-1236
increases VEGFR-3 protein expression and that, by directly binding to VEGFR-3, it enhances VEGFR-3 endocytosis and stability.

Conclusion—
Our in vivo and in vitro results provide the first insight into the mechanism by which AIP1 mediates VEGFR-3–dependent angiogenic and lymphangiogenic signaling.
Comparative genomics of enterohemorrhagic Escherichia coli O145:H28 demonstrates a common evolutionary lineage with Escherichia coli O157:H7
Authors: Cooper Kerry K , Mandrell Robert E , Louie Jacqueline W , Korlach Jonas , Clark Tyson A , Parker Craig T , Huynh Steven , Chain Patrick S , Ahmed Sanaa , Carter Michelle Qiu 
Published: January 2014

Abstract

Background
Although serotype O157:H7 is the predominant enterohemorrhagic Escherichia coli (EHEC), outbreaks of non-O157 EHEC that cause severe foodborne illness, including hemolytic uremic syndrome have increased worldwide. In fact, non-O157 serotypes are now estimated to cause over half of all the Shiga toxin-producing Escherichia coli (STEC) cases, and outbreaks of non-O157 EHEC infections are frequently associated with serotypes O26, O45, O103, O111, O121, and O145. Currently, there are no complete genomes for O145 in public databases.

Results
We determined the complete genome sequences of two O145 strains (EcO145), one linked to a US lettuce-associated outbreak (RM13514) and one to a Belgium ice-cream-associated outbreak (RM13516). Both strains contain one chromosome and two large plasmids, with genome sizes of 5,737,294 bp for RM13514 and 5,559,008 bp for RM13516. Comparative analysis of the two EcO145 genomes revealed a large core (5,173 genes) and a considerable amount of strain-specific genes. Additionally, the two EcO145 genomes display distinct chromosomal architecture, virulence gene profile, phylogenetic origin of Stx2a prophage, and methylation profile (methylome). Comparative analysis of EcO145 genomes to other completely sequenced STEC and other E. coli and Shigella genomes revealed that, unlike any other known non-O157 EHEC strain, EcO145 ascended from a common lineage with EcO157/EcO55. This evolutionary relationship was further supported by the pangenome analysis of the 10 EHEC str ains. Of the 4,192 EHEC core genes, EcO145 shares more genes with EcO157 than with the any other non-O157 EHEC strains.

Conclusions
Our data provide evidence that EcO145 and EcO157 evolved from a common lineage, but ultimately each serotype evolves via a lineage-independent nature to EHEC by acquisition of the core set of EHEC virulence factors, including the genes encoding Shiga toxin and the large virulence plasmid. The large variation between the two EcO145 genomes suggests a distinctive evolutionary path between the two outbreak strains. The distinct methylome between the two EcO145 strains is likely due to the presence of a Bsu BI/Pst I methyltransferase gene cassette in the Stx2a prophage of the strain RM13514, suggesting a role of horizontal gene transfer-mediated epigenetic alteration in the evolution of individual EHEC strains.
Specific CT 3D rendering of the treatment zone after Irreversible Electroporation (IRE) in a pig liver model: the “Chebyshev Center Concept” to define the maximum treatable tumor size
Authors: Vollherbst Dominik , Fritz Stefan , Zelzer Sascha , Wachter Miguel F , Wolf Maya B , Stampfl Ulrike , Gnutzmann Daniel , Bellemann Nadine , Schmitz Anne , Knapp Jürgen , Pereira Philippe L , Kauczor Hans U , Werner Jens , Radeleff Boris A , Sommer Christof M 
Published: January 2014

Abstract

Background
Size and shape of the treatment zone after Irreversible electroporation (IRE) can be difficult to depict due to the use of multiple applicators with complex spatial configuration. Exact geometrical definition of the treatment zone, however, is mandatory for acute treatment control since incomplete tumor coverage results in limited oncological outcome. In this study, the “Chebyshev Center Concept” was introduced for CT 3d rendering to assess size and position of the maximum treatable tumor at a specific safety margin.

Methods
In seven pig livers, three different IRE protocols were applied to create treatment zones of different size and shape: Protocol 1 (n = 5 IREs), Protocol 2 (n = 5 IREs), and Protocol 3 (n = 5 IREs). Contrast-enhanced CT was used to assess the treatment zones. Technique A consisted of a semi-automated software prototype for CT 3d rendering with the “Chebyshev Center Concept” implemented (the “Chebyshev Center” is the center of the largest inscribed sphere within the treatment zone) with automated definition of parameters for size, shape and position. Technique B consisted of standard CT 3d analysis with manual definition of the same parameters but position.

Results
For Protocol 1 and 2, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were not significantly different between Technique A and B. For Protocol 3, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were significantly smaller for Technique A compared with Technique B (41.1 ± 13.1 mm versus 53.8 ± 1.1 mm and 39.0 ± 8.4 mm versus 53.8 ± 1.1 mm; p < 0.05 and p < 0.01). For Protocol 1, 2 and 3, sphericity of the treatment zone was significantly larger for Technique A compared with B.

Conclusions
Regarding size and shape of the treatment zone after IRE, CT 3d rendering with the “Chebyshev Center Concept” implemented provides significantly different results compared with standard CT 3d analysis. Since the latter overestimates the size of the treatment zone, the “Chebyshev Center Concept” could be used for a more objective acute treatment control.
Four-year analysis of cataract surgery rates in Shanghai, China: a retrospective cross-sectional study
Authors: Zhu Mingming , Zhu Jianfeng , Lu Lina , He Xiangui , Zhao Rong , Zou Haidong 
Published: January 2014

Abstract

Background
The cataract surgery rate (CSR) is a critical index used to show that cataract blindness is being eliminated. It is considered to be tightly connected to social economic development; however, it is still extremely low in developing countries such as China. Although Shanghai is the most economically developed city in China, its CSR and the obstacles for increasing its CSR have not been previously evaluated.

Methods
A retrospective cross-sectional study was conducted. By analyzing the data in the “Shanghai Cataract Operations Database” from 2006 to 2009, the CSR in Shanghai was calculated. The numbers of cataract surgeries between urban and suburban districts as well as among various medical institutions were compared.

Results
The CSR in Shanghai increased from 1741 in 2006 to 2210 in 2009, reflecting a 26.94% improvement. Phacoemulsification was the most frequent surgical choice for cataract removal, accounting for 94.93% of total cataract surgeries by 2009. In addition, by 2009, the CSR in urban districts had reached 5468, but only 532 in the suburbs. During 2009, cataract surgery records in 68 district hospitals, 23 medical centers, and 6 private hospitals comprised 32.05%, 52.33%, and 15.62%, respectively, of the total. There was a nearly 3.3-fold increase in the number of surgeries performed in private hospitals in the past four years. Furthermore, the average number of cataract surgeries per doctor that took place in private hospitals per year reached 207, which exceeded the average of 145 that took place in medical centers.

Conclusions
Until 2009, the CSR in Shanghai remained below the rates of social development and fell short of targets suggested by the World Health Organization (WHO). Furthermore, increasing the CSR in the suburbs as well as in district hospitals is an important issue that needs to be addressed.
Reciprocal regulation of MicroRNA-99a and insulin-like growth factor I receptor signaling in oral squamous cell carcinoma cells
Authors: Yen Yi-Chen , Shiah Shine-Gwo , Chu Hsiao-Chien , Hsu Yuan-Ming , Hsiao Jenn-Ren , Chang Jang-Yang , Hung Wen-Chun , Liao Chun-Ta , Cheng Ann-Joy , Lu Ya-Ching , Chen Ya-Wen 
Published: January 2014

Abstract

Background
MicroRNAs (miRNAs), small noncoding RNA molecules can function as oncogenes or tumor suppressors in tumorigenesis. Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide with a 5-year survival rate of approximately 50%.

Methods
The expression of microRNA-99a (miR-99a) in OSCC tissues and cell lines was investigated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. The functions of miR-99a in migration/invasion and lung colonization were determined by transwell and tail vein injection assays, respectively. Specific targets of miR-99a were determined by software prediction, correlation with target protein expression, and luciferase reporter assay. The signaling pathways involved in regulation of miR-99a were investigated using the kinase inhibitors.

Results
We observed reduced levels of miR-99a, identified as one of the most downregulated miRNA in OSCC and all tested OSCC cell lines compared to normal oral keratinocytes. Ectopic miR-99a expression in OSCC cells markedly reduced migration and invasion in vitro as well as lung colonization in vivo. When evaluating the specific targets of miR-99a, we found that ectopic miR-99a expression downregulates insulin-like growth factor 1 receptor (IGF1R) protein and that the expression of miR-99a correlates negatively with IGF1R protein in OSCC cells. Insertion of the 3′UTR of IGF1R mRNA into the 3′UTR of a reporter gene markedly reduced luciferase activity in OSCC cells expressing miR-99a, suggesting that miR-99a reduces luciferase activity by targeting the 3′UTR of IGF1R mRNA. When evaluating the mechanisms of miR-99a downregulation, we observed the upregulation of miR-99a expression in serum-starved conditions and its suppression in response to insulin-like growth factor (IGF1) stimulation. Inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) kinase inhibited IGF1-induced suppression of miR-99a, suggesting the negative regulation of miR-99a expression by IGF1R signaling.

Conclusion
Overall, results indicate that miR-99a functions as a tumor metastasis suppressor in OSCC cells and mutually regulates IGF1R expression in a reciprocal regulation.
Hematologic and biochemical reference intervals for specific pathogen free 6-week-old Hampshire-Yorkshire crossbred pigs
Authors: Cooper Caitlin A , Moraes Luis E , Murray James D , Owens Sean D 
Published: January 2014

Abstract

Background
Hematologic and biochemical reference intervals depend on many factors, including age. A review of the literature highlights the lack of reference intervals for 6-wk-old specific pathogen free (SPF) Hampshire-Yorkshire crossbred pigs. For translational research, 6-wk-old pigs represent an important animal model for both human juvenile colitis and diabetes mellitus type 2 given the similarities between the porcine and human gastrointestinal maturation process. The aim of this study was to determine reference intervals for hematological and biochemical parameters in healthy 6-wk-old crossbred pigs. Blood samples were collected from 66 clinically healthy Hampshire-Yorkshire pigs. The pigs were 6 wks old, represented both sexes, and were housed in a SPF facility. Automated hematological and biochemical analysis were performed using an ADVIA 120 Hematology System and a Cobas 6000 C501 Clinical Chemistry Analyzer.

Results
Reference intervals were calculated using both parametric and nonparametric methods. The mean, median, minimum, and maximum values were calculated.

Conclusion
As pigs are used more frequently as medical models of human disease, having reference intervals for commonly measured hematological and biochemical parameters in 6-wk-old pigs will be useful. The reference intervals calculated in this study will aid in the diagnosis and monitoring of both naturally occurring and experimentally induced disease. In comparison to published reference intervals for older non SPF pigs, notable differences in leukocyte populations, and in levels of sodium, potassium, glucose, protein, and alkaline phosphatase were observed.
Singing Resources to Help Teach Foreign Language at Primary School
Authors: Саакян  , Saakyan Sona 
Published: January 2014

Educating potential of singing resources in teaching
foreign language to primary school students is revealed.
Emphasized are phonetic, lexical and grammatical aspects
of teaching resource of songs. It is pointed that songs as
educational material also help students to develop
communication skills, give them linguistic and countryspecific
knowledge, improve general and musical culture
and strengthen motivation. The author outlines a real case
where pupils have successfully mastered some Englishlanguage
grammatical units, pretty difficult for perception
of lower-grades students, based on the song, involving
different grammatical forms of the verb “to be”.
Researches of Biogas Composition on Landfill
Authors: Масликов  , Maslikov V. , Чусов  , Chusov A. , Молодцов  , Molodtsov D. 
Published: January 2014

A practical experience related to execution of work on landfills in order to obtain information on spatial distribution of
biogas’s main components in different areas of waste disposal for landfill site zoning depending on biogas saturation
degree, for energy potential assessment and creation of degassing systems for justification of remediation has been
considered in this paper.
Effect of metabolic abnormalities on cognitive performance and clinical symptoms in schizophrenia
Authors: Wysokiński Adam , Dzienniak Małgorzata , Kłoszewska Iwona 
Published: January 2014

Aim of the studyThe objective of this study is to determine whether and how metabolic abnormalities are associated with clinical symptoms and cognitive performance in schizophrenia.Subject or material and methods46 adult patients with schizophrenia taking first- or second generation antipsychotics were included in the study. The following data were collected: BMI, abdominal circumference, lipid panel and blood glucose, blood pressure and treatment of comorbidities. Clinical symptoms were assessed using PANSS, CDSS, CGI and SAS scales. Cognitive performance was assessed using CNS Vital Signs computerized battery of tests: Verbal Memory test, Visual Memory test, Finger Tapping Test, Symbol Digit Coding, Stroop Test, Shifting Attention Test, and Continuous Performance Test.ResultsDyslipidemia, raised LDL and raised blood glucose levels were the best predictors of more severe clinical symptoms (PANSS, PANSS P, PANSS G, CGI) and lower neurocognitive index, worse cognitive flexibility, executive functions, complex attention composite memory, verbal memory, slower reaction time and worse performance in SAT, CPT, ST tests. Obesity was associated with worse results in VBM, VIM, FTT, SDC tests. Raised blood pressure was associated with improvements in all cognitive domains and better performance in SAT, CPT, ST tests.DiscussionThere are several weak associations between severity of clinical symptoms and metabolic abnormalities. Most of these were for blood glucose levels and raised blood glucose. Lipids and glucose abnormalities are the best predictors of deteriorated cognitive performance. Contrary to previous observations, raised blood pressure was associated with better results in cognitive tests.ConclusionsThese findings indicate that cognitive impairment and metabolic abnormalities may be linked in patients with schizophrenia.
On types of matrices and centralizers of matrices and permutations
Authors: Britnell John R. , Wildon Mark 
Published: January 2014

Abstract
It is known that the centralizer of a matrix
over a finite field depends, up to conjugacy, only on the type of the
matrix, in the sense defined by J. A. Green.
In this paper an analogue of the type invariant is defined that
in general captures more information; using this invariant the
result on centralizers is extended to arbitrary fields.
The converse is also proved: thus two matrices have conjugate centralizers
if and only if they have the same generalized type.
The paper ends with the analogous results for symmetric and alternating groups.
Reconstruction of interfaces using CGO solutions for the Maxwell equations
Authors: Kar Manas , Sini Mourad 
Published: January 2014

Abstract.
We deal with the problem of reconstructing interfaces using complex geometrical optics solutions for the Maxwell system.
The contributions are twofold.
First, we justify the enclosure method for the impenetrable obstacle case avoiding any assumption on the directions of the phases
of the CGOs (or the curvature of obstacle's surface). In addition, we need only a Lipschitz regularity of this surface.
The analysis is based on some fine properties of the corresponding layer potentials in appropriate Sobolev spaces.
Second, we justify this method also for the penetrable case, where the interface is modeled by the jump (or the discontinuity)
of the magnetic permeability μ. A key point of the analysis is the global Lp
-estimates for the curl of the solutions of the Maxwell system with discontinuous
coefficients. These estimates are justified here for p near 2 generalizing to the Maxwell case the well-known Meyers's Lp
-estimates
of the gradient of the solution of scalar divergence form elliptic problems.
Identification of a constant coefficient in a quasi-linear elliptic equation
Authors: Lyubanova Anna S. 
Published: January 2014

Abstract.
The identification of an unknown constant
coefficient in the main term of the second order differential
equation

-
k
M
(
|
u

|

p
-
2

u
)
+
g

(
x
)

u
=
f

(
x
)

${ - kM(|u|^{p-2} u) + g(x) u = f(x) }$

with Dirichlet boundary
condition is considered. The elliptic operator M is self-adjoint,

p
≥
2

${p \ge 2}$

.
The identification of k here is based on an
integral boundary data. The local existence and uniqueness theorems
for the inverse problem is proved in the class of the pairs
involving a function u such that

|
u
|

p
-
2

u
∈

W
2
2

(
Ω
)

${|u|^{p-2} u \in W^2_2 (\Omega )}$

and a positive real number k.
A data-smoothing approach to explore and test gene-environment interaction in case-parent trios
Authors: Shin Ji-Hyung , Infante-Rivard Claire , McNeney Brad , Graham Jinko 
Published: January 2014

AbstractComplex traits result from an interplay between genes and environment. A better understanding of their joint effects can help refine understanding of the epidemiology of the trait. Various tests have been proposed to assess the statistical interaction between genes and the environment (
The BAG Homology Domain of Snl1 Cures Yeast Prion [URE3] Through Regulation of Hsp70 Chaperones
Authors: Kumar Navinder , Gaur Deepika , Masison Daniel C , Sharma Deepak 
Published: January 2014

AbstractThe BAG family of proteins is evolutionarily conserved from yeast to humans and plants. In animals and plants, the BAG family possesses multiple members with overlapping and distinct functions that regulate many cellular processes, such as signaling, protein degradation, and stress response. The only BAG domain protein in Saccharomyces cerevisiae is Snl1, which is anchored to the endoplasmic reticulum through an amino-terminal transmembrane region. Snl1 is the only known membrane-associated nucleotide exchange factor for 70-kilodalton heat shock protein (Hsp70), and thus its role in regulating cytosolic Hsp70 functions is not clear. Here, we examine whether Snl1 regulates Hsp70 activity in the propagation of stable prion-like protein aggregates. We show that unlike other nucleotide exchange factors, Snl1 is not required for propagation of yeast prions [URE3] and [PSI+]. Overexpressing Snl1 derivative consisting of only the BAG domain (Snl1-S) cures [URE3]; however, elevated levels of the entire cytosolic domain of Snl1 (Snl1-M), which has nine additional amino-terminal residues, has no effect. Substituting the three lysine residues in this region of Snl1-M with alanine restores ability to cure [URE3]. [PSI+] is unaffected by overproduction of either Snl1-S or Snl1-M. The Snl1-S mutant engineered with weaker affinity to Hsp70 does not cure [URE3], indicating that curing of [URE3] by Snl1-S requires Hsp70. Our data suggest that Snl1 anchoring to endoplasmic reticulum or nuclear membrane restricts its ability to modulate cytosolic activities of Hsp70 proteins. Furthermore, the short amino-terminal extension of the BAG domain profoundly affects its function.