bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superparamagnetic iron oxide nanoparticles mediated 131I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice
Authors: Chen Jing , Zhu Shu , Tong Liangqian , Li Jiansha , Chen Fei , Han Yunfeng , Zhao Ming , Xiong Wei 
Published: February 2014

Abstract

Background
Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (131I) against the human vascular endothelial growth factor (hVEGF).

Methods
hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment.

Results

131I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control.

Conclusions
EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging.
Causes of death and associated risk factors among climacteric women from Southern Brazil: a population based-study
Authors: Colpani Verônica , Oppermann Karen , Spritzer Poli Mara 
Published: February 2014

Abstract

Background
Aging and menopause are particular cardiovascular risk factors for women, due to estrogen deprivation at the time of menopause. Studies show that diabetes mellitus (DM), smoking, hypertension, high body mass index (BMI), and serum lipids are associated with increased risk of cardiovascular disease (CVD), the main cause of female mortality in Brazil. The aim of this study was to assess the mortality rate, causes of death and associated risk factors in a cohort of women from Brazil.

Methods
A longitudinal population-based study of menopausal status is currently underway in a city in South Brazil. In 2010, a third follow-up of this population was performed to assess cardiovascular risk and mortality rate between 1995 and 2011. For this analysis, 358 participants were studied. At baseline, participants had completed a standardized questionnaire including demographic, lifestyle, medical and reproductive characteristics. In addition to the contacts with relatives, mortality data were obtained through review of medical records in all city hospitals and the Center for Health Information (NIS/RS-SES). Multivariate-adjusted hazard risk (HR) and 95% confidence intervals (CI95%) were estimated using Cox proportional hazards regression. Survival curves were estimated using the Kaplan-Meier curve.

Results
There were 17 (4.7%) deaths from all causes during the study period. Seven (41.2%) deaths were caused by CVD, including four cases of stroke and three cases of myocardial infarction. Six (35.3%) deaths were due to cancer, and four (23.5%) were due to other reasons. In the age and smoking-adjusted multivariate models, diabetes (HR 6.645, 95% CI: 1.938–22.79, p = 0.003), alcohol intake (HR 1.228, 95% CI: 1.014-1.487, p = 0.035) and postmenopausal status (HR = 6.216, 95% CI: 0.963–40.143, p = 0.055) were associated with all-cause mortality. A significant association was found between abdominal obesity (WHR ≥ 0.85) and mortality even after the adjustment for BMI (HR = 9.229, 95% IC: 2.083–41.504, p = 0.003).

Conclusion
CVD was an important cause of mortality in this cohort and DM and/or central adiposity were associated with all-cause mortality. Lifestyle and dietary factors seem to be related to risk of mortality in middle-aged women.
Differences in virulence of pneumolysin and autolysin mutants constructed by insertion duplication mutagenesis and in-frame deletion in Streptococcus pneumoniae
Authors: Liu Esther Yip-Mei , Chang Feng-Yee , Chang Jen-Chang , Fung Chang-Phone 
Published: February 2014

Abstract

Background
Insertion duplication mutagenesis (IDM) and in-frame deletion (IFD) are common techniques for studying gene function, and have been applied to pneumolysin (ply), a virulence gene in Streptococcus pneumoniae (D39). Discrepancies in virulence between the two techniques were observed in both the previous and present studies. This phenomenon was also observed during mutation analysis of autolysin (lytA).

Results
Our data showed that target gene restoration (TGR) occurred in IDM mutants, even in the presence of antibiotics, while the IFD mutants were stable. In PCR result, TGR occurred later in IDM-ply and -lytA mutants cultured in non-supplemented medium (4–5 h) compared with those grown in medium supplemented with erythromycin (erm)/chloramphenicol (cat) (3–4 h), but plateaued faster. Real-time PCR for detecting TGR had been performed. When compared with 8-h culture, TGR detection increased from Day 1 and Day 2 of IDM mutant’s culture. erm-sensitive clones from IDM mutant were found. Southern blot hybridization and Western blotting also confirmed the phenomenon of TGR. The median survival of mice following intraperitoneal (IP) injection with a 3-h culture of IDM-mutants was significantly longer than that with an 8-h culture, irrespective of antibiotic usage. The median survival time of mice following IP injection of a 3-h culture versus an 8-h culture of IDM-ply in the absence of antibiotics was 10 days versus 2 days (p = 0.031), respectively, while in the presence of erm, the median survival was 5 days versus 2.5 days (p = 0.037), respectively. For an IDM-lytA mutant, the corresponding values were 8.5 days versus 2 days (p = 0.019), respectively, for non-supplemented medium, and 2.5 versus 2 days (p = 0.021), respectively, in the presence of cat. A comparable survival rate was observed between WT D39 and an 8-h IDM culture.

Conclusion
TGR in IDM mutants should be monitored to avoid inconsistent results, and misinterpretation of data due to TGR could lead to important biological meaning being overlooked. Therefore, based on these results, IFD is preferable to IDM for disruption of target genes.
Zyflamend, a polyherbal mixture, down regulates class I and class II histone deacetylases and increases p21 levels in castrate-resistant prostate cancer cells
Authors: Huang E-Chu , Zhao Yi , Chen Guoxun , Baek Seung Joon , McEntee Michael F , Minkin Steven , Biggerstaff John P , Whelan Jay 
Published: February 2014

Abstract

Background
Zyflamend, a mixture containing extracts of ten herbs, has shown promise in a variety of preclinical cancer models, including prostate cancer. The current experiments were designed to investigate the effects of Zyflamend on the expression of class I and II histone deacetylases, a family of enzymes known to be over expressed in a variety of cancers.

Methods
CWR22Rv1 cells, a castrate-resistant prostate cancer cell line, were treated with Zyflamend and the expression of class I and II histone deacetylases, along with their downstream target the tumor suppressor gene p21, was investigated. Involvement of p21 was confirmed with siRNA knockdown and over expression experiments.

Results
Zyflamend down-regulated the expression of all class I and II histone deacetylases where Chinese goldthread and baikal skullcap (two of its components) appear to be primarily responsible for these results. In addition, Zyflamend up regulated the histone acetyl transferase complex CBP/p300, potentially contributing to the increase in histone 3 acetylation. Expression of the tumor suppressor gene p21, a known downstream target of histone deacetylases and CBP/p300, was increased by Zyflamend treatment and the effect on p21 was, in part, mediated through Erk1/2. Knockdown of p21 with siRNA technology attenuated Zyflamend-induced growth inhibition. Over expression of p21 inhibited cell growth and concomitant treatment with Zyflamend enhanced this effect.

Conclusions
Our results suggest that the extracts of this polyherbal combination increase histone 3 acetylation, inhibit the expression of class I and class II histone deacetylases, increase the activation of CBP/p300 and inhibit cell proliferation, in part, by up regulating p21 expression.
On mappings with φ-contractive iterate at a point on generalized metric spaces
Authors: Gajić Ljiljana , Stojaković Mila 
Published: February 2014

Abstract
We prove a set of fixed point theorems for mappings with φ-contractive iterate at a point in a class of generalized metric spaces. This is a generalization of some well-known results for Guseman and Matkowski types of fixed point results in metric and generalized metric spaces.

MSC:47H10, 54H25.
Common fixed points for weak commutative mappings on a multiplicative metric space
Authors: He Xiaoju , Song Meimei , Chen Danping 
Published: February 2014

Abstract
In this paper, we discuss the unique common fixed point of two pairs of weak commutative mappings on a complete multiplicative metric space. They satisfy the following inequality:

d
(
S
x
,
T
y
)
≤

{
max
{
d
(
A
x
,
B
y
)
,
d
(
A
x
,
S
x
)
,
d
(
B
y
,
T
y
)
,
d
(
S
x
,
B
y
)
,
d
(
A
x
,
T
y
)
}
}

λ

, where A and S are weak commutative, B and T also are weak commutative. Our results substantially generalize and extend the results of Özavsar and Cevikel (Fixed point of multiplicative contraction mappings on multiplicative metric space).

MSC:46B20, 47A12.
An online tool for mapping insecticide resistance in major Anopheles vectors of human malaria parasites and review of resistance status for the Afrotropical region
Authors: Knox Tessa B , Juma Elijah O , Ochomo Eric O , Pates Jamet Helen , Ndungo Laban , Chege Patrick , Bayoh Nabie M , N’Guessan Raphael , Christian Riann N , Hunt Richard H , Coetzee Maureen 
Published: February 2014

Abstract

Background
Malaria control programmes across Africa and beyond are facing increasing insecticide resistance in the major anopheline vectors. In order to preserve or prolong the effectiveness of the main malaria vector interventions, up-to-date and easily accessible insecticide resistance data that are interpretable at operationally-relevant scales are critical. Herein we introduce and demonstrate the usefulness of an online mapping tool, IR Mapper.

Methods
A systematic search of published, peer-reviewed literature was performed and Anopheles insecticide susceptibility and resistance mechanisms data were extracted and added to a database after a two-level verification process. IR Mapper (http://www.irmapper.com) was developed using the ArcGIS for JavaScript Application Programming Interface and ArcGIS Online platform for exploration and projection of these data.

Results
Literature searches yielded a total of 4,084 susceptibility data points for 1,505 populations, and 2,097 resistance mechanisms data points for 1,000 populations of Anopheles spp. tested via recommended WHO methods from 54 countries between 1954 and 2012. For the Afrotropical region, data were most abundant for populations of An. gambiae, and pyrethroids and DDT were more often used in susceptibility assays (51.1 and 26.8% of all reports, respectively) than carbamates and organophosphates. Between 2001 and 2012, there was a clear increase in prevalence and distribution of confirmed resistance of An. gambiae s.l. to pyrethroids (from 41 to 87% of the mosquito populations tested) and DDT (from 64 to 91%) throughout the Afrotropical region. Metabolic resistance mechanisms were detected in western and eastern African populations and the two kdr mutations (L1014S and L1014F) were widespread. For An. funestus s.l., relatively few populations were tested, although in 2010–2012 resistance was reported in 50% of 10 populations tested. Maps are provided to illustrate the use of IR Mapper and the distribution of insecticide resistance in malaria vectors in Africa.

Conclusions
The increasing pyrethroid and DDT resistance in Anopheles in the Afrotropical region is alarming. Urgent attention should be afforded to testing An. funestus populations especially for metabolic resistance mechanisms. IR Mapper is a useful tool for investigating temporal and spatial trends in Anopheles resistance to support the pragmatic use of insecticidal interventions.
Familial testicular germ cell tumor: no associated syndromic pattern identified
Authors: Mueller Christine M , Korde Larissa A , McMaster Mary L , Peters June A , Bratslavsky Gennady , Watkins Rissah J , Ling Alex , Kratz Christian P , Wulfsberg Eric A , Rosenberg Philip S , Greene Mark H 
Published: February 2014

AbstractBackgroundTesticular germ cell tumor (TGCT) is the most common malignancy in young men. Familial clustering, epidemiologic evidence of increased risk with family or personal history, and the association of TGCT with genitourinary (GU) tract anomalies have suggested an underlying genetic predisposition. Linkage data have not identified a rare, highly-penetrant, single gene in familial TGCT (FTGCT) cases. Based on its association with congenital GU tract anomalies and suggestions that there is an intrauterine origin to TGCT, we hypothesized the existence of unrecognized dysmorphic features in FTGCT.MethodsWe evaluated 38 FTGCT individuals and 41 first-degree relatives from 22 multiple-case families with detailed dysmorphology examinations, physician-based medical history and physical examination, laboratory testing, and genitourinary imaging studies.ResultsThe prevalence of major abnormalities and minor variants did not significantly differ between either FTGCT individuals or their first-degree relatives when compared with normal population controls, except for tall stature, macrocephaly, flat midface, and retro-/micrognathia. However, these four traits were not manifest as a constellation of features in any one individual or family. We did detect an excess prevalence of the genitourinary anomalies cryptorchidism and congenital inguinal hernia in our population, as previously described in sporadic TGCT, but no congenital renal, retroperitoneal or mediastinal anomalies were detected.ConclusionsOverall, our study did not identify a constellation of dysmorphic features in FTGCT individuals, which is consistent with results of genetic studies suggesting that multiple low-penetrance genes are likely responsible for FTGCT susceptibility.
Free amino acid content in breast milk of adolescent and adult mothers in Ecuador
Authors: Baldeón Manuel E , Mennella Julie A , Flores Nancy , Fornasini Marco , San Gabriel Ana 
Published: February 2014

Abstract
Because of increased incidence of teenage births and high prevalence of lactation in Latin America, we determined the patterning of free amino acids (FAAs) in breast milk of 65 primiparous Ecuadorian women of varying ages (14–27 years). An automatic amino acid analyzer quantified levels of FAAs in milk samples obtained at three lactation stages: colostrum, transition, and mature milk. Regardless of mother’s age, most FAAs increased with time postpartum, with taurine, glutamic acid, glutamine, and alanine being most abundant in all stages.
Effect of ambient storage on the quality characteristics of aerobically packaged fish curls incorporated with different flours
Authors: Raja Waseem Hussain , Kumar Sunil , Bhat Zuhaib Fayaz , Kumar Pavan 
Published: February 2014

Abstract
The present study was conducted to evaluate the effect of ambient storage on the quality attributes of aerobically packaged fish curls incorporated with optimum levels of different flours. The curls were developed by extrusion technology using fish meat (Catla catla). The fish curls containing optimum levels of different flours viz. 20 percent corn flour, 10 percent black gram flour and 10 percent peanut flour were compared with the control snacks containing 30 percent rice flour and assessed for storage quality and shelf life at ambient temperature. The curls were aerobically packaged in LDPE (low density polyethylene) pouches and evaluated for various physicochemical, microbiological and sensory parameters. Mean values of pH of all the curls showed significantly (p < 0.05) decreasing trend with increasing days of storage (6.34 ± 0.01 on day 0 and 5.90 ± 0.005 on day 28 for control samples, 6.41 ± 0.009 on day 0 and 6.11 ± 0.02 on day 28 for corn flour incorporated samples, 6.36 ± 0.01 on day 0 and 6.14 ± 0.01 on day 28 for black gram flour incorporated samples, 6.57 ± 0.007 on day 0 and 6.34 ± 0.01 on day 28 for peanut flour incorporated samples). TBARS (mg malonaldehyde/kg), total plate count (log cfu/g) and yeast and mould count (log cfu/g) for the control as well as treatment samples showed significantly (p < 0.05) increasing trend with storage. Coliform counts (log cfu/g) were not detected until day 28 in all the products. The mean scores of sensory parameters i.e. appearance and colour, flavor, crispiness, texture and overall acceptability for control as well as treatment samples showed significantly (p < 0.05) decreasing trend with storage period. The decrease was significantly (p < 0.05) highest on 21st and 28th day of storage. The mean values for all the quality and storage parameters up to the day 21 of the storage were within the acceptable limits. Thus, based on various physicochemical and sensory parameters, the curls incorporated with optimum level of different flours were acceptable up to 21 days of ambient storage within the LDPE pouches.
Neutrophils mediate edema formation but not mechanical allodynia during zymosan-induced inflammation
Authors: Suo Jing , Linke Bona , Meyer dos Santos Sascha , Pierre Sandra , Stegner David , Zhang Dong Dong , Denis Cecile V , Geisslinger Gerd , Nieswandt Bernhard , Scholich Klaus 
Published: February 2014

ABSTRACTInflammatory pain is based on stimulation and sensitization of peripheral endings of sensory neurons (nociceptors) by pronociceptive mediators. These mediators can be released by resident cells, as well as invading immune cells. Although neutrophils are known to release various mediators, which can stimulate or sensitize nociceptors, the extent of their contribution to nociceptive responses is unclear. Here, we studied the contribution of neutrophils to zymosan-induced inflammatory pain, which is characterized by an early recruitment of high numbers of neutrophils. Surprisingly, antibody-mediated neutrophil depletion caused a complete loss of edema formation but had no effect on mechanical pain thresholds. Blockage of the interaction between neutrophils and platelets or endothelial cells using antibodies directed against CD11b and CD162 reduced neutrophil recruitment to the site of inflammation. Again, the treatment decreased zymosan-induced edemas without altering mechanical pain thresholds. Also, HLB-219 mice, which have five to 10 times less platelets than WT mice, showed reduced neutrophil recruitment to the site of inflammation and decreased edema sizes, whereas, again, mechanical thresholds were unaltered. The effects observed in HLB-219 mice were relatively small and not reproduced in vWF-deficient mice or after antibody-mediated blockage of GPIbα. Flow chamber and transmigration assays showed that platelets were not necessary for neutrophil adhesion to endothelial cells but increased their transmigration. Taken together, zymosan-induced mechanical allodynia is, in contrast to edema formation, independent of neutrophils, and recruitment of neutrophils is only partly influenced by interactions with platelets.
Three-dimensional distribution of igneous rocks near the Pebble porphyry Cu-Au-Mo deposit in southwestern Alaska: Constraints from regional-scale aeromagnetic data
Authors: Anderson Eric D. , Zhou Wei , Li Yaoguo , Hitzman Murray W. , Monecke Thomas , Lang James R. , Kelley Karen D. 
Published: February 2014

Aeromagnetic data helped us to understand the 3D distribution of plutonic rocks near the Pebble porphyry copper deposit in southwestern Alaska, USA. Magnetic susceptibility measurements showed that rocks in the Pebble district are more magnetic than rocks of comparable compositions in the Pike Creek–Stuyahok Hills volcano-plutonic complex. The reduced-to-pole transformation of the aeromagnetic data demonstrated that the older rocks in the Pebble district produce strong magnetic anomaly highs. The tilt derivative transformation highlighted northeast-trending lineaments attributed to Tertiary volcanic rocks. Multiscale edge detection delineated near-surface magnetic sources that are mostly outward dipping and coalesce at depth in the Pebble district. The total horizontal gradient of the 10-km upward-continued magnetic data showed an oval, deep magnetic contact along which porphyry deposits occur. Forward and inverse magnetic modeling showed that the magnetic rocks in the Pebble district extend to depths greater than 9 km. Magnetic inversion was constrained by a near-surface, 3D geologic model that is attributed with measured magnetic susceptibilities from various rock types in the region. The inversion results indicated that several near-surface magnetic sources with moderate susceptibilities converge with depth into magnetic bodies with higher susceptibilities. This deep magnetic source appeared to rise toward the surface in several areas. An isosurface value of 0.02 SI was used to depict the magnetic contact between outcropping granodiorite and nonmagnetic sedimentary host rocks. The contact was shown to be outward dipping. At depths around 5 km, nearly the entire model exceeded the isosurface value indicating the limits of nonmagnetic host material. The inversion results showed the presence of a relatively deep, northeast-trending magnetic low that parallels lineaments mapped by the tilt derivative. This deep low represents a strand of the Lake Clark fault.