bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular definition of the pro‐tumorigenic phenotype of glioma‐activated microglia
Authors: Ellert‐Miklaszewska Aleksandra , Dabrowski Michal , Lipko Maciej , Sliwa Marcin , Maleszewska Marta , Kaminska Bozena
Published: May 2013

Microglia are myeloid cells residing in the central nervous system that participate in inflammatory responses and could promote injury and repair. Gliomas attract microglia and polarize them into tumor‐supporting cells that participate in matrix remodeling, invasion, angiogenesis, and suppression of adaptive immunity. Although signaling pathways and critical regulators underlying classical inflammation are well established, signal transduction and transcriptional circuits underlying the alternative activation of microglia are poorly known. Using primary rat microglial cultures exposed to glioma conditioned medium or lipopolysaccharide (LPS), we demonstrate that microglia adapt different fates and polarize into pro‐inflammatory or alternatively activated cells. Glioma‐derived factors increased cell motility, phagocytosis, and sustained proliferation of microglial cells that was mediated by enhanced focal adhesion kinase and PI‐3K/Akt signaling. The signals from glioma cells induced ERK and p38 MAPK but not JNK signaling and failed to activate pro‐inflammatory Stat1 and NFκB signaling in microglial cells. Transcriptome analysis of microglial cultures at 6 h after exposure to glioma‐conditioned medium or LPS revealed different patterns of gene expression. Glioma‐induced activation was associated with induction of genes coding for ID (inhibitor of DNA binding) 1/3 and c‐Myc, markers of the alternative phenotype Arg1, MT1‐MMP, CXCL14, and numerous cytokines/chemokines implicated in immune cell trafficking. Many classical inflammation‐related genes and signaling pathways failed to be induced. Our study indicates for the first time molecular pathways that direct microglia toward the pro‐invasive, immunosuppressive phenotype.
Long‐term treatment with Sitagliptin, a dipeptidyl peptidase‐4 inhibitor, reduces colon carcinogenesis and reactive oxygen species in 1,2‐dimethylhydrazine‐induced rats
Authors: Femia Angelo Pietro , Raimondi Laura , Maglieri Giulia , Lodovici Maura , Mannucci Edoardo , Caderni Giovanna
Published: May 2013

Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) increase colon cancer risk. Antidiabetic drugs stabilizing incretin hormones, such as inhibitors of dipeptidyl peptidase‐4 activity (DPP4i), may affect colon carcinogenesis; however, the data remain controversial. Therefore, the authors studied whether long‐term administration of the DPP4i Sitagliptin (SITA) affects 1,2‐dimethylhydrazine (DMH)‐induced colon carcinogenesis. Male F344 rats fed a high‐fat (HF) diet promoting colon carcinogenesis and IR, were induced with DMH (100 mg/kg × 2 times). One week later, the animals were allocated to two groups: one continuing with HF diet (controls; n = 8) and one receiving SITA (n = 8) mixed in the diet (260 ppm). Body weight, food consumption and glycemia were not affected by SITA. Fifteen weeks after DMH, the number of the precancerous lesions mucin‐depleted foci (MDF) was significantly lower in rats treated with SITA [MDF/colon: 9.5 ± 0.9 and 6.4 ± 0.9 in controls (n = 8) and SITA groups (n = 8), respectively; means ± SE, p < 0.05]. Reactive oxygen species in the blood were also significantly lower in the SITA group [6.75 ± 0.69 and 5.63 ± 0.75 (H2O2 in mM) in controls (n = 5) and SITA (n = 6), respectively; means ± SE, p < 0.05]. Rats treated with SITA had a lower DPP4 activity in the intestine but not in the plasma. Intestine growth morphometric parameters and colon proliferation, as proliferating cell nuclear antigen expression, were not affected by SITA. In conclusion, the results suggest a protective effect of DPP4i against colon carcinogenesis that could be exploited in chemoprevention trials.
Estrogen and insulin‐like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice
Authors: Tang Hexiao , Liao Yongde , Xu Liqiang , Zhang Chao , Liu Zhaoguo , Deng Yu , Jiang Zhixiao , Fu Shengling , Chen Zhenguang , Zhou Sheng
Published: May 2013

Estrogen receptor (ER) and insulin‐like growth factor‐1 receptor (IGF‐1R) signaling are implicated in lung cancer progression. Based on their previous findings, the authors sought to investigate whether estrogen and IGF‐1 act synergistically to promote lung adenocarcinoma (LADE) development in mice. LADE was induced with urethane in ovariectomized Kunming mice. Tumor‐bearing mice were divided into seven groups: 17β‐estradiol (E2), E2+fulvestrant (Ful; estrogen inhibitor), IGF‐1, IGF‐1+AG1024 (IGF‐1 inhibitor), E2+IGF‐1, E2+IGF‐1+Ful+AG1024 and control groups. After 14 weeks, the mice were sacrificed, and then the tumor growth was determined. The expression of ERα/ERβ, IGF‐1, IGF‐1R and Ki67 was examined using tissue‐microarray‐immunohistochemistry, and IGF‐1, p‐ERβ, p‐IGF‐1R, p‐MAPK and p‐AKT levels were determined based on Western blot analysis. Fluorescence‐quantitative polymerase chain reaction was used to detect the mRNA expression of ERβ, ERβ2 and IGF‐1R. Tumors were found in 93.88% (46/49) of urethane‐treated mice, and pathologically proven LADE was noted in 75.51% (37/49). In the E2+IGF‐1 group, tumor growth was significantly higher than in the E2 group (p < 0.05), the IGF‐1 group (p < 0.05) and control group (p < 0.05). Similarly, the expression of ERβ, p‐ERβ, ERβ2, IGF‐1, IGF‐1R, p‐IGF‐1R, p‐MAPK, p‐AKT and Ki67 at the protein and/or mRNA levels was markedly higher in the ligand group than in the ligand + inhibitor groups (all p < 0.05). This study demonstrated for the first time that estrogen and IGF‐1 act to synergistically promote the development of LADE in mice, and this may be related to the activation of the MAPK and AKT signaling pathways in which ERβ1, ERβ2 and IGF‐1R play important roles.
Calcium‐binding protein expression in peritoneal endometriosis‐associated nerve fibres
Authors: Barcena de Arellano M. L. , Münch S. , Arnold J. , Helbig S. , Schneider A. , Mechsner S.
Published: May 2013

Background

Recent studies demonstrated the potential involvement of nerve fibres in the chronic inflammatory process of endometriosis. We aimed to characterize nerve fibres in the proximal and distal areas of the peritoneal endometriotic lesions in order to understand the chronic inflammatory process in endometriosis.

Methods

Peritoneal endometriotic lesions (proximal area) (n = 17), the matching unaffected peritoneum (distal area) and healthy peritoneum of patients without endometriosis (n = 15) were analysed with the neuronal markers PGP 9.5, calbindin, calretinin and parvalbumin. Peritoneal fluids of women with and without endometriosis were used for Western blot analysis and for the neuronal growth assay. The protein expression of neuronal PC‐12 cells incubated with peritoneal fluids was analysed.

Results

The overall nerve fibre density was significantly reduced in the distal area of the lesion when compared with the proximal area or with healthy peritoneum. The density of calbindin‐, calretinin‐ and parvalbumin‐positive nerve fibres was significantly increased in the endometriosis group. Calretinin expression was elevated in the peritoneal fluid of women with symptomatic endometriosis when compared with women with asymptomatic endometriosis. Furthermore, PC‐12 cells incubated with peritoneal fluid of women with endometriosis showed a higher proliferation rate and a stronger neurite outgrowth than the control group. PC‐12 cells incubated in peritoneal fluids of women with endometriosis expressed less calretinin but more calbindin than the control group.

Conclusions

Calcium‐binding proteins seem to be increased in endometriosis‐associated nerve fibres and might play an important role in the chronic inflammatory condition and the pain pathogenesis of endometriosis.
Long‐term antinociception by electroacupuncture is mediated via peripheral opioid receptors in free‐moving rats with inflammatory hyperalgesia
Authors: Wang Y. , Hackel D. , Peng F. , Rittner H. L.
Published: May 2013

Background

Electroacupuncture (EA) has been widely accepted and applied as an important acupuncture‐related technique for acupuncture analgesia (AA) research. The involvement of opioid peptides and receptors in acute AA has been shown via pre‐EA application of opioid receptor/peptide antagonists. In this study, we intended to reproducibly institute acupoint position and needling excluding influences from anaesthesia or restrainers on rats with complete Freund's adjuvant (CFA) hind paw inflammatory pain, as well as to explore opioid‐dependency and anti‐inflammatory effects in sustained acupuncture analgesia.

Methods

Accurate position and needling approach on acupoint GB30 was modelled by computer‐based three‐dimensional (3D) images and followed by an optimal EA treatment protocol (100 Hz, 2–3 mA, 20 min) at 0 and 24 h post‐CFA in conscious free‐moving rats. Opioid receptor antagonists, naloxone (NLX) and naltrindole (NTI) were applied intraplantarly post‐EA at late phase (96 h) of CFA. Nociceptive thresholds were assessed by paw pressure threshold (Randall‐Sellito) or paw withdrawal latency (Hargreaves), and anti‐inflammatory effects were evaluated by measurement of plantar temperature and paw volume.

Results

EA elicited significant sustained mechanical and thermal antinociception up to 144 h. Mechanical antinociception of EA was suppressed by peripheral intraplantar application of NLX and NTI. EA also reduced paw temperature and volume during the same time frame indicating anti‐inflammatory effects.

Conclusions

By employing a reproducible EA treatment model on GB30 in free‐moving rats, we demonstrated the involvement of peripheral opioid receptors mediated EA‐induced long‐term antinociception. Future studies should examine the specific neuroimmunological connection of EA‐induced sustained antinociception in inflammation.
Thrombospondin‐4 contributes to spinal cord injury‐induced changes in nociception
Authors: Zeng J. , Kim D. , Li K.‐W. , Sharp K. , Steward O. , Zaucke F. , Luo Z.D.
Published: May 2013

Background

Our previous data have indicated that nerve injury‐induced up‐regulation of thrombospondin‐4 (TSP4) proteins in dorsal spinal cord plays a causal role in neuropathic pain state development in a spinal nerve ligation model. To investigate whether TSP4 proteins also contribute to the development of centrally mediated changes in nociception after spinal cord injury (SCI), we investigated whether SCI induced TSP4 dysregulation, and if so, whether this change correlated with changes in nociception in a T9 spinal cord contusion injury model.

Methods

Behavioural sensitivity to mechanical, thermal stimuli and locomotor function recovery were tested blindly in SCI or sham rats post‐injury. Intrathecal antisense or mismatch control oligodeoxynucleotides were used to treat SCI rats with nociceptive hyperreflexia, and Western blots were used to measure TSP4 protein levels in dorsal spinal cord samples.

Results

SCI induced below‐level hindpaw hypersensitivity to stimuli. TSP4 protein levels are up‐regulated in dorsal spinal cord of SCI rats with nociceptive hyperreflexia, but not in SCI rats without nociceptive hyperreflexia. There was no significant difference in motor function recovery post‐injury between SCI rats with or without nociceptive hyperreflexia. Intrathecal treatment with TSP4 antisense, but not mismatch control, oligodeoxynucleotides led to reversal of injury‐induced TSP4 up‐regulation and nociceptive hyperreflexia in SCI rats.

Conclusions

SCI leads to TSP4 up‐regulation in lumbar spinal cord that may play a critical role in mediating centrally mediated behavioural hypersensitivity. Blocking this pathway may be helpful in management of SCI‐induced changes in nociception.
A novel approach to identify responder subgroups and predictors of response to low‐ and high‐dose capsaicin patches in postherpetic neuralgia
Authors: Martini C.H. , Yassen A. , Krebs‐Brown A. , Passier P. , Stoker M. , Olofsen E. , Dahan A.
Published: May 2013

Background

Treatment of chronic pain conditions is commonly assessed at specific endpoints at preset times during or after treatment by analysis of the total study population. An alternative approach is the identification of specific patient subgroups characterized by differential response patterns in their analgesic response and to determine the presence of significant predictors of effect.

Methods

Data from four double‐blind, randomized controlled trials on the efficacy of topical capsaicin 8% (Qutenza) versus an active control (capsaicin 0.04%) in patients with postherpetic neuropathic pain were combined. Longitudinal pharmacodynamic, mixture and covariate analyses were performed on the pooled dataset.

Results

Data from 1248 patients treated with Qutenza (n = 722) or topical low‐dose capsaicin 0.04% (n = 526) were successfully analysed. Five distinct response subgroups were detected with different treatment efficacies, including a group of non‐responders, a group showing partial analgesic effect and a group showing full analgesic effect. Active control and Qutenza had similar response profiles, but the proportional distribution of patients among the five response groups was in favour of Qutenza, with 40% less non‐responders and 25% more patients showing a full analgesic response. For Qutenza, important predictors of efficacy were efficacy of lidocaine pretreatment and greater pretreatment pain score variability.

Conclusions

The analyses indicate the existence of different response groups to treatment with Qutenza and an active control patch that may possibly be related to different pain mechanisms among these groups, despite a presumed common underlying disease process, and that require different treatment approaches among subgroups.
Application of a rotating bioreactor consisting of low‐cost and ready‐to‐use medical disposables for in vitro evaluation of the endothelialization efficiency of small‐caliber vascular prostheses
Authors: Avci‐Adali Meltem , Kobba Joseph , Neumann Bernd , Lescan Mario , Perle Nadja , Wilhelm Nadja , Wiedmaier Hartmut , Schlensak Christian , Wendel Hans Peter
Published: May 2013

The incomplete endothelialization of especially small‐caliber vascular prostheses after implantation in patients is a major disadvantage in cardiovascular interventions. The lack of an endothelium leads to the occurrence of thrombosis at the luminal surface of artificial vascular prostheses. Thus, the development of new graft materials and coatings for induction of complete endothelialization on the implant surfaces is a promising approach to improve hemocompatibility and maintain long‐term graft patency. In this study, we designed a rotation model to evaluate the early endothelial cell (EC) seeding efficiency of different small‐caliber vascular devices, such as stents and vascular grafts. The suitability of the designed rotation model for endothelialization studies was investigated by seeding and cultivation of prostheses with ECs followed by scanning electron microscopy. Furthermore, the viability of attached ECs was determined by calcein acetoxymethyl ester (AM) staining. The rotation model consisting of low‐cost medical disposables enabled sterile incubation and cultivation of ECs with vascular devices. Simultaneously, the rotation of the bioreactor ensured a uniform distribution and adhesion of cells to the devices. Calcein AM staining of adherent cells on prostheses revealed excellent cell viability. Moreover, using the designed rotation model, an influence of different coatings and materials on the adhesion and spreading of ECs was demonstrated. The rotating bioreactor described and used in this study not only saves time and money but is also eminently useful for the accelerated preclinical evaluation of the endothelialization efficiency of different materials and surface coatings of small‐caliber vascular devices. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Statistical analysis of an ionospheric parameter as a base for earthquake prediction
Authors: Li Mei , Parrot Michel
Published: May 2013

This paper is related to the use of ionospheric density variations to tentatively predict earthquakes. The results of this statistical analysis are presented as a function of various parameters. The ion density was recorded by the low‐altitude satellite DEMETER during more than 6 years, and a search for anomalies was automatically conducted with the complete data set. In a second time, a software checked if each anomaly could correspond to an earthquake. The search was conducted at less than 1500 km from the anomaly positions, and until 15 days after the anomaly time. The earthquakes have been classified depending on their magnitude, depth, and position (below the sea or inland). This attempt to predict earthquakes of course generates a lot of false alarms and wrong detections. Nevertheless, it is shown that the number of good detections increases with the magnitude of the earthquakes. In average the number of perturbations is higher the day of the earthquake, and then smoothly decreases for the days before. Earthquakes below the sea are better detected. There are seismic areas close to the South Atlantic Magnetic Anomaly and at high latitudes where the number of natural perturbations is too important to expect a high number of good detections. Finally, when there are several perturbations corresponding to a single earthquake, it is possible to combine their positions to have a better estimation of the location of the future epicenter. However, uncertainties about the time and the magnitude are large.
The source of the Canary current in fall 2009
Authors: Pérez‐Hernández M. Dolores , Hernández‐Guerra Alonso , Fraile‐Nuez Eugenio , Comas‐Rodríguez Isis , Benítez‐Barrios Verónica M. , Domínguez‐Yanes J. Francisco , Vélez‐Belchí Pedro , De Armas Demetrio
Published: May 2013

The source of the Canary Current has been inferred from an inverse box model applied to the hydrographic data of a survey carried out in 2009 in the northeast subtropical gyre (29–37°N, 9–24°W). The Portugal Current is observed between 13.5 and 14.8°W at 37°N carrying
Sv southward. This current presumably merges with the eastward transport of the Azores Current System and partly contributes to the Mediterranean inflow and partly to the northward recirculation of the Azores Current through the Gulf of Cadiz. The Azores Current System is located in the meridional range 33.50–36.25°N at 24.50°W. This System transports eastward
Sv in the thermocline layers and
Sv at intermediate layers. The Azores Current intermediate water mass has the highest portion of Sub‐Arctic intermediate water (SAIW) in the region, while the Azores Countercurrent intermediate waters mass is mainly Mediterranean water. The Canary Current extends from 22.25° to 18.50°W at 29°N, the westernmost position ever observed. This current transports southward
Sv in the thermocline layers and
Sv in the intermediate layers. This intermediate flow shows a relative maximum of oxygen and a relative minimum in nutrient concentration, indicating the presence of SAIW. The study concludes that, at least in fall 2009, the Canary Current extends to the intermediate waters (
approximately 1600 dbar) and that Azores Current feeds the Canary Current at surface and intermediate layers.
Decadal prediction of the dominant West African monsoon rainfall modes
Authors: García‐Serrano J. , Doblas‐Reyes F. J. , Haarsma R. J. , Polo I.
Published: May 2013

The present study offers for the first time the validation of decadal prediction systems upon the West African monsoon (WAM) variability. The ENSEMBLES multimodel and perturbed parameter decadal reforecasts are used to assess multiyear prediction skill for the dominant WAM precipitation regimes. Thus, the focus of the assessment is on time scales longer than seasonal to interannual. To retain lower‐frequency predictability (interannual to decadal), a 4 year average is applied, which indeed has been shown to remove most of the interannual variability that is unpredictable beyond 1 year in dynamical forecasting (e.g., El Niño–Southern Oscillation). First, the decadal hindcasts are analyzed to assess forecast skill of Guinean and Sahelian area‐averaged rainfall indices. Findings suggest that there is no significant skill in predicting these rainfall indices, probably due to the distinctive representations of deep tropical convection in each forecast system. This is further addressed by computing and comparing the leading modes of WAM variability in the ENSEMBLES decadal reforecasts against observations. Results show that while in the observations, global warming has an important role, in the forecast systems, the Atlantic Ocean is the main player. The Atlantic Niño represents the leading forcing for the simulated Guinean precipitation. Sea surface temperature (SST) anomalies associated with the simulated Sahelian precipitation project onto the Atlantic multidecadal variability (AMV), in which the subtropical branch shows consistency across the forecast systems. No significant skill has been found, however, to predict these WAM precipitation modes, although the Sahelian pattern presents systematic positive correlation scores and lower root mean square errors along the whole forecast range. This is reflected in a tendency for reproducing the Sahel dry period around the 1980s. Likewise, the good performance across the models in simulating the relationship between the leading rainfall modes and the surrounding SST forcings points out encouraging prospects for decadal forecasting. Previous studies show multiyear prediction skill of the AMV in the ENSEMBLES decadal reforecasts. Here the skill of the Atlantic‐3 SST index is discussed.
The curious case of Mercury's internal structure
Authors: Hauck Steven A. , Margot Jean‐Luc , Solomon Sean C. , Phillips Roger J. , Johnson Catherine L. , Lemoine Frank G. , Mazarico Erwan , McCoy Timothy J. , Padovan Sebastiano , Peale Stanton J. , Perry Mark E. , Smith David E. , Zuber Maria T.
Published: May 2013

The recent determination of the gravity field of Mercury and new Earth‐based radar observations of the planet's spin state afford the opportunity to explore Mercury's internal structure. These observations provide estimates of two measures of the radial mass distribution of Mercury: the normalized polar moment of inertia and the fractional polar moment of inertia of the solid portion of the planet overlying the liquid core. Employing Monte Carlo techniques, we calculate several million models of the radial density structure of Mercury consistent with its radius and bulk density and constrained by these moment of inertia parameters. We estimate that the top of the liquid core is at a radius of 2020 ± 30 km, the mean density above this boundary is 3380 ± 200 kg m−3, and the density below the boundary is 6980 ± 280 kg m−3. We find that these internal structure parameters are robust across a broad range of compositional models for the core and planet as a whole. Geochemical observations of Mercury's surface by MESSENGER indicate a chemically reducing environment that would favor the partitioning of silicon or both silicon and sulfur into the metallic core during core‐mantle differentiation. For a core composed of Fe–S–Si materials, the thermodynamic properties at elevated pressures and temperatures suggest that an FeS‐rich layer could form at the top of the core and that a portion of it may be presently solid.
Parkinson's disease cybrids, differentiated or undifferentiated, maintain morphological and biochemical phenotypes different from those of control cybrids
Authors: Appukuttan T.A. , Ali N. , Varghese M. , Singh A. , Tripathy D. , Padmakumar M. , Gangopadhyay P.K. , Mohanakumar K.P.
Published: May 2013

SH‐SY5Y, control, and Parkinson's disease (PD) cybrids prepared from an Indian population were differentiated using retinoic acid (RA) for understanding their dopaminergic characteristics and neuritogenesis. Undifferentiated control and PD cybrids exhibited higher levels of TH mRNA, but lower c‐RET expression, short neurites, low neuritic density, and low proportion of cells with neurites compared with the undifferentiated parent cell line, SH‐SY5Y. The expression levels of DAT and Ptx3 were similar to SH‐SY5Y. PD cybrids showed poor viability and lower differentiating potency than SH‐SY5Y or control cybrids. RA treatment for 6 days elevated c‐RET expression and corrected the neuritic morphology of the control, but not of PD cybrids. Cell viability was found to be reduced in differentiated control and PD cybrids. TH expression level was significantly elevated in SH‐SY5Y following RA treatment, but not in both the cybrids. In differentiated control and PD cybrids, the TH immunofluorescence intensity was significantly lower compared with SH‐SY5Y cells. MitoTracker Green fluorescence intensity of the mitochondria was higher in differentiated PD cybrids. Dopamine released into the medium was unaffected in the differentiated SH‐SY5Y or in the control cybrids but was significantly elevated in PD cybrids. These results suggest that PD cybrids, differentiated or undifferentiated, maintained morphological and biochemical phenotypes significantly different from those of the control cybrids, or the differentiated SH‐SY5Y cells, and therefore could be an ideal cellular model of the disease for pharmacological screening of drugs and for investigation of the pathophysiology of PD. © 2013 Wiley Periodicals, Inc.
Effect of whey protein hydrolysates with different molecular weight on fatigue induced by swimming exercise in mice
Authors: Liu Jing , Wang Xinxia , Zhao Zheng
Published: May 2013

BACKGROUND

In order to improve the antioxidant and anti‐fatigue capacities of whey protein for wider utilization, it was hydrolyzed by chymotrypsin (EC 3.4.21.1) to produce whey protein hydrolysate (WPH). Fractions of WPH with different molecular weight (MW) were separated by ultrafiltration. Kunming mice in various treatment groups were orally administered (1.5 g kg−1 body weight) whey protein isolate (WPI), WPH or WPHs with different MW (<5, 5–10, 10–30 or >30 kDa) for 6 weeks to explore whether different MW fractions of WPH affected mice fatigue.

RESULTS

Compared with the control group (orally administered 9 g kg−1 saline) or the WPI group, low‐MW (<10 kDa) WPH groups showed prolonged swimming time (P < 0.05) and had higher concentrations (P < 0.05) of glucose, non‐esterfied fatty acid, liver glycogen, superoxide dismutase and glutathione peroxidase and lower concentration of lactate. Low‐MW (<10 kDa) WPHs had higher hydroxyl‐ and α,α‐diphenyl‐β‐picrylhydrazyl‐scavenging abilities and ferrous‐chelating capacity than WPI.

CONCLUSION

The results proved that low‐MW (<10 kDa) WPHs with higher anti‐fatigue capacity showed higher free radical‐scavenging and ferrous‐chelating activities. © 2013 Society of Chemical Industry
Microbiological quality and characteristics of probiotic products in China
Authors: Chen Tingtao , Wu Qinglong , Li Shengjie , Xiong Shunqiang , Jiang Shuying , Tan Qianglai , Zhang Zhichao , Zhu Daochen , Wei Hua
Published: May 2013

BACKGROUND

Probiotics are widely used in the food industry and medicine fields in China, but few studies have been conducted to evaluate the actual microbial amounts and species in probiotic products, which may conflict with the labels and mislead consumers to choose inappropriate foods or medicines.

RESULTS

Twenty commercial dairy products and eight commercial ‘healthcare’ samples were collected from markets in China and tested using culture‐dependent and culture‐independent methods. The results suggested that the total bacterial counts of most commercial products met the minimum quantitative requirement of the Chinese national standard (6.00 log colony‐forming units g−1). However, the bacterial counts of specific species were inconsistent with the labelling. In parallel, denaturing gradient gel electrophoresis analysis indicated that some probiotic‐containing products were wrongly labelled; no Bifidobacterium species were detected in the products claiming to contain bifidobacteria, and the probiotic characteristics (antimicrobial activity, acid resistance and bile resistance) of some isolates had degraded. Moreover, some contaminating bacteria, e.g. Enterobacter sp., Klebsiella sp. and Serratia sp., were also detected in these products.

CONCLUSION

The combination of culture‐dependent and culture‐independent methods was proven to quickly and conveniently detect the microbial diversity in probiotic products, and more effort is required to regulate the probiotic market in China. © 2013 Society of Chemical Industry
Ultrasound Sonication Effects on Silk Fibroin Protein
Authors: Samal Sangram K. , Kaplan David L. , Chiellini Emo
Published: May 2013

The utilization of silk fibroin protein (SFP) in the field of biomaterials and tissue engineering plays an important role due to its promising mechanical, biological, and processing properties. In the present study, SFP solutions were exposed to ultrasound sonication to assess impact on molecular weight (Mw), sol–gel transition behavior, and physico‐chemical properties. The Mw of SFP was significantly reduced with sonication, determined by sodium dodecyl sulfate polyacrylamide gels (SDS–PAGE) gel electrophoresis. Sol–gel transitions were observed as SFP assembled to form a reversible SFP gel network at different concentrations and sonication time with the formation of a β‐sheet‐rich conformation in the gel state. The conformational changes and morphological properties were correlated over a range of SFP concentrations by circular dichroism (CD), UV spectroscopy, swelling and attenuated total reflectance fourier transformed infrared spectroscopy (ATR‐FTIR).

magnified image
Effect of white adipose tissue flap and insulin‐like growth factor‐1 on nerve regeneration in rats
Authors: Kilic Ayhan , Ojo Bukola , Rajfer Rebecca A. , Konopka Geoffrey , Hagg Daniel , Jang Eugene , Akelina Yelena , Mao Jeremy J. , Rosenwasser Melvin P. , Tang Peter
Published: May 2013

Adipose tissue‐derived stem cells and insulin‐like growth factor‐1 (IGF‐1) have shown potential to enhance peripheral nerve regeneration. The purpose of this study was to investigate the effect of an in vivo biologic scaffold, consisting of white adipose tissue flap (WATF) and/or IGF‐1 on nerve regeneration in a crush injury model. Forty rats all underwent a sciatic nerve crush injury and then received: a pedicled WATF, a controlled local release of IGF‐1, both treatments, or no treatment at the injury site. Outcomes were the normalized maximum isometric tetanic force (ITF) of the tibialis anterior muscle and histomorphometric measurements. At 4 weeks, groups with WATF had a statistically significant improvement in maximum ITF recovery, as compared to those without (P < 0.05), and there was an increase in myelin thickness and total axon count in the WATF‐only group versus control (P < 0.01). Functional and histomorphometric data suggest that IGF‐1 suppressed the effect of the WATF. Use of a pedicled WATF improved the functional and histomorphometrical results after axonotmesis in a rat model. IGF‐1 does not appear to enhance nerve regeneration in this model. Utilizing the WATF may have a beneficial therapeutic role in peripheral nerve injuries. © 2013 Wiley Periodicals, Inc. Microsurgery 33:367–375, 2013.
A modified method for processing and characterization of organoclay‐based poly(ethylene terephthalate) nanocomposite fibers
Authors: Turan Dilek , Sirin Humeyra , Gurdag Sezen , Ozkoc Guralp
Published: May 2013

In the current study, in order to prepare poly(ethylene terephthalate) (PET)/organoclay nanocomposite fibers, a slurry‐compounding method (SCM) was applied and compared to conventional melt‐compounding method (CMM) in terms of the dispersion of organoclays and the performance of the spun and or drawn fibers. The organoclays were synthesized by using three different alkyl phosphonium salts and compared with commercially available alkyl ammonium‐modified organoclays in terms of thermal stability and basal spacing. It was found that the alkyl phosphonium salts exhibited higher thermal stability and basal spacing with respect to commercial alkyl ammonium organoclays. Among them, tributylhexadecylphosphonium bromide resulted in superior properties; therefore, it was used to prepare the nanocomposite PET fibers. The organoclay content of 0.1–1 wt% was taken as the material parameter. It was demonstrated that the SCM yielded better dispersion of organoclays with respect to CMM. The drawn nanocomposite fibers prepared via SCM exhibited improved tensile strength and modulus in comparison to the neat‐PET. The maximum tensile properties for fibers were obtained at 0.5% organoclay loading in SCM. The thermal properties and the percentage of crystallinity were investigated by differential scanning calorimetry analysis. In addition, Fourier transform infrared spectroscopy was utilized to obtain the percentage of crystallinity of the fibers. POLYM. COMPOS., 34:887–896, 2013. © 2013 Society of Plastics Engineers
A miniature condensed‐phase membrane introduction mass spectrometry (CP‐MIMS) probe for direct and on‐line measurements of pharmaceuticals and contaminants in small, complex samples
Authors: Duncan Kyle D. , Willis Megan D. , Krogh Erik T. , Gill Christopher G.
Published: May 2013

RATIONALE

High‐throughput, automated analytical measurements are desirable in many analytical scenarios, as are rapid sample pre‐screening techniques to identify 'positive' samples for subsequent measurements using more time‐consuming conventional methodologies (e.g., liquid chromatography/mass spectrometry (LC/MS)). A miniature condensed‐phase membrane introduction mass spectrometry (CP‐MIMS) probe for the direct and continuous, on‐line measurement of pharmaceuticals and environmental contaminants in small, complex samples is presented.

METHODS

A miniature polydimethylsiloxane hollow fibre membrane (PDMS‐HFM) probe is coupled with an electrospray ionization (ESI) triple quadrupole mass spectrometer. Analytes are transported from the probe to the ESI source by a methanol acceptor phase. The probe can be autosampler mounted and directly inserted in small samples (≥400 μL) allowing continuous and simultaneous pptr–ppb level detection of target analytes (chlorophenols, triclosan, gemfibrozil, nonylphenol) in complex samples (artificial urine, beer, natural water, waste water, plant tissue).

RESULTS

The probe has been characterized and optimized for acceptor phase flow rate, sample mixing and probe washing. Signal response times, detection limits and calibration data are given for selected ion monitoring (SIM) and tandem mass spectrometry (MS/MS) measurements of target analytes at trace levels. Comparisons with flow cell type CP‐MIMS systems are given. Analyte depletion effects are evaluated for small samples (≥400 μL). On‐line measurements in small volumes of complex samples, temporally resolved reaction monitoring and in situ/in vivo demonstrations are presented.

CONCLUSIONS

The miniature CP‐MIMS probe developed was successfully used for the direct, on‐line detection of target analytes in small volumes (40 mL to 400 μL) of complex samples at pptr to low ppb levels. The probe can be readily automated as well as deployed for in situ/in vivo monitoring, including reaction monitoring, small sample measurements and direct insertion in living plant tissue. Copyright © 2013 John Wiley & Sons, Ltd.
Applicability of non‐linear versus linear fractional abundance calibration plots for the quantitative determination of triacylglycerol regioisomers by tandem mass spectrometry
Authors: Ramaley Louis , Herrera Lisandra Cubero , Melanson Jeremy E.
Published: May 2013

RATIONALE

Regioisomeric analysis of triacylglycerols is important in understanding lipid biochemistry and the involvement of lipids in disease and nutrition. The use of calibration plots employing fractional abundances provides a simple and rapid method for such analyses. These plots are believed to be linear, but evidence exists for non‐linearity. The behavior of such plots needs to be understood to allow for proper interpretation of regioisomeric data.

METHODS

Solutions of five regioisomer pairs were prepared from pure standards and used to construct calibration plots using triple‐stage tandem mass spectrometry (MS3) with electrospray ionization (ESIMS3) and cationization by lithium ions. The data were taken by direct infusion with an AB SCIEX QTRAP 2000 QqLIT mass spectrometer.

RESULTS

Non‐linear calibration plots were observed for the four isomer pairs containing the polyunsaturated eicosapentaenoic (20:5) and docosahexaenoic (22:6) acids paired with palmitic acid (16:0) or myristic acid (14:0), while the pair including palmitic and stearic (18:0) acids provided a linear plot. A non‐linear model was developed for these plots and then verified experimentally.

CONCLUSIONS

The fractional abundance calibration plots used in regioisomeric analysis of triacylglycerols are intrinsically non‐linear, but may appear linear if the scatter in data points obscures the curvature, if the curvature is slight, or if the response factors for the two isomers in the regioisomer pair are similar. Therefore, linearity should not be assumed for these types of measurements until confirmed experimentally. Copyright © 2013 John Wiley & Sons, Ltd.
Concise Review: Pursuing Self-Renewal and Pluripotency with the Stem Cell Factor Nanog
Authors: Saunders Arven , Faiola Francesco , Wang Jianlong
Published: May 2013

Pluripotent embryonic stem cells and induced pluripotent stem cells hold great promise for future use in tissue replacement therapies due to their ability to self-renew indefinitely and to differentiate into all adult cell types. Harnessing this therapeutic potential efficiently requires a much deeper understanding of the molecular processes at work within the pluripotency network. The transcription factors Nanog, Oct4, and Sox2 reside at the core of this network, where they interact and regulate their own expression as well as that of numerous other pluripotency factors. Of these core factors, Nanog is critical for blocking the differentiation of pluripotent cells, and more importantly, for establishing the pluripotent ground state during somatic cell reprogramming. Both mouse and human Nanog are able to form dimers in vivo, allowing them to preferentially interact with certain factors and perform unique functions. Recent studies have identified an evolutionary functional conservation among vertebrate Nanog orthologs from chick, zebrafish, and the axolotl salamander, adding an additional layer of complexity to Nanog function. Here, we present a detailed overview of published work focusing on Nanog structure, function, dimerization, and regulation at the genetic and post-translational levels with regard to the establishment and maintenance of pluripotency. The full spectrum of Nanog function in pluripotent stem cells and in cancer is only beginning to be revealed. We therefore use this evidence to advocate for more comprehensive analysis of Nanog in the context of disease, development, and regeneration.
Hes1 Desynchronizes Differentiation of Pluripotent Cells by Modulating STAT3 Activity
Authors: Zhou Xinzhi , Smith Andrew J.H. , Waterhouse Anna , Blin Guillaume , Malaguti Mattias , Lin Chia-Yi , Osorno Rodrigo , Chambers Ian , Lowell Sally
Published: May 2013

Robust development of the early embryo may benefit from mechanisms that ensure that not all pluripotent cells differentiate at exactly the same time: such mechanisms would build flexibility into the process of lineage allocation. This idea is supported by the observation that pluripotent stem cells differentiate at different rates in vitro. We use a clonal commitment assay to confirm that pluripotent cells commit to differentiate asynchronously even under uniform differentiation conditions. Stochastic variability in expression of the Notch target gene Hes1 has previously been reported to influence neural versus mesodermal differentiation through modulation of Notch activity. Here we report that Hes1 also has an earlier role to delay exit from the pluripotent state into all lineages. The early function of Hes1 to delay differentiation can be explained by an ability of Hes1 to amplify STAT3 responsiveness in a cell-autonomous manner. Variability in Hes1 expression therefore helps to explain why STAT3 responsiveness varies between individual ES cells, and this in turn helps to explain why pluripotent cells commit to differentiate asynchronously.
Connexins, gap junctions, and glia
Authors: Giaume Christian , Naus Christian C.
Published: May 2013

Neurons and glial cells are the two main classes of cells present in brain. There are four classes of glial cells in the brain that differ by their origin, morphology, and function: microglia, oligodendrocytes, NG2 (nerve/glia antigen 2) cells, and astrocytes. Microglial cells, which are derived from the mesoderm, represent approximately 10% of glia and are the resident immune cells of the central nervous system (CNS). Three subclasses compose the macroglia and are derived from the ectoderm. As an overview one can consider that: (1) the oligodendrocytes are mainly involved in the myelination of axons, (2) the NG2 cells comprise oligodendrocyte precursor cells but they are also multipotential cells, although this issue is still debated, and (3) finally, astrocytes are the predominant glial cells in the brain that establish active interactions with neurons and the vascular system. With the exception of NG2 cells, all glial cells are characterized by the expression of gap junction proteins (connexins) with specific features and properties. In addition, a number of neuropathological disorders involve changes in Cx expression and channel function. WIREs Membr Transp Signal 2013, 2:133–142. doi: 10.1002/wmts.87

Conflict of interest: The authors have declared no conflicts of interest for this article.

For further resources related to this article, please visit the WIREs website.
Metabolite sensing in eukaryotic mRNA biology
Authors: Clingman Carina C. , Ryder Sean P.
Published: May 2013

All living creatures change their gene expression program in response to nutrient availability and metabolic demands. Nutrients and metabolites can directly control transcription and activate second‐messenger systems. More recent studies reveal that metabolites also affect post‐transcriptional regulatory mechanisms. Here, we review the increasing number of connections between metabolism and post‐transcriptional regulation in eukaryotic organisms. First, we present evidence that riboswitches, a common mechanism of metabolite sensing in bacteria, also function in eukaryotes. Next, we review an example of a double stranded RNA modifying enzyme that directly interacts with a metabolite, suggesting a link between RNA editing and metabolic state. Finally, we discuss work that shows some metabolic enzymes bind directly to RNA to affect mRNA stability or translation efficiency. These examples were discovered through gene‐specific genetic, biochemical, and structural studies. A directed systems level approach will be necessary to determine whether they are anomalies of evolution or pioneer discoveries in what may be a broadly connected network of metabolism and post‐transcriptional regulation. WIREs RNA 2013, 4:387–396. doi: 10.1002/wrna.1167

This article is categorized under:

RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition

RNA Interactions with Proteins and Other Molecules > Small Molecule–RNA Interactions

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

Regulatory RNAs/RNAi/Riboswitches > Riboswitches
Developing a new shock‐collar design for safe and efficient use on wild wolves
Authors: Hawley Jason E. , Rossler Shawn T. , Gehring Thomas M. , Schultz Ronald N. , Callahan Peggy A. , Clark Raymond , Cade Jerry , Wydeven Adrian P.
Published: May 2013

Electronic training collars, or shock collars, have received relatively little application as a non‐lethal management tool for reducing livestock losses caused by gray wolves (Canis lupus). One of the major obstacles to using shock collars on wolves has been the lack of a safe and efficient collar design. We developed a new shock‐collar design and tested it for safety and efficacy on captive wolves. Our design used a radiocollar with a shock unit mounted on the back. Shock units were fitted with rounded probes that contact the back of a wolf's shaved neck and with externally mounted batteries to increase battery life. We tested our design in 5 different captive trials conducted during 2003–2005 at the Wildlife Science Center, Minnesota, USA, and eliminated neck damage shown in previous shock‐collar research, while retaining the ability to effectively deliver a shock. We extended battery life to 80 days. We believe this new shock‐collar design could be used as a safe and efficient alternative to lethal control in certain situations for wild wolves. © 2013 The Wildlife Society.
Trauma in Canada: A Spirit of Equity & Collaboration
Authors: Zakrison Tanya , Ball Chad G. , Kirkpatrick Andrew W.
Published: May 2013

Background

The delivery of equitable trauma care in Canada is not without challenges within our universal health care system. Notably, the tyranny of geography is intermittently at odds with adequate access for our rural, indigenous, and impoverished populations. Other differences exist when compared with neighbouring trauma systems, for example in the United States.

Methods

As a critical review, we chose to compare and critique the overall system of trauma organization and perceived societal expectations of a high‐income, North American country (Canada) to assist with discussions on trauma systems for the future.

Results

Tele‐technology is providing some early solutions. Trauma systems and delivery of care in Canada differ from the United States due to our single‐payer system, regionalization and universal provision. Care for injured Canadians has a long history of being multidisciplinary, with collaborative research programs. Canada also has a history of global surgical endeavours, beginning with Dr. Norman Bethune and his recognition of the political causes of trauma and continuing as a global public health concern for all.

Conclusions

While challenges continue to exist for the provision of equitable trauma care in Canada, unique multidisciplinary, collaborative and technology‐based solutions continue to be developed, both locally and globally, to address this critical public health issue.