Engineering E. coli for Magnetic Control and the Spatial Localization of Functions.

The fast-developing field of synthetic biology enables broad applications of programmed microorganisms including the development of whole-cell biosensors, delivery vehicles for therapeutics, or diagnostic agents. However, the lack of spatial control required for localizing microbial functions could limit their use and induce their dilution leading to ineffective action or dissemination. To overcome this limitation, the integration of magnetic properties into living systems enables a contact-less and orthogonal method for spatiotemporal control. Here, we generated a magnetic-sensing Escherichia coli by driving the formation of iron-rich bodies into bacteria. We found that these bacteria could be spatially controlled by magnetic forces and sustained cell growth and division, by transmitting asymmetrically their magnetic properties to one daughter cell. We combined the spatial control of bacteria with genetically encoded-adhesion properties to achieve the magnetic capture of specific target bacteria as well as the spatial modulation of human cell invasions.

Self-assembly of magnetically-functionalized molecular motors and microtubules into active gels.

The diversity of functions achieved by living cells result from the collective behavior of biological components that interact through multiple scales in time and space. The cytoskeleton constitutes one canonical system forming dynamic organizations when interacting with molecular motors. These materials constitute a state of active matter that exhibit out-of-equilibrium behavior with oriented order in the presence of energy. However, such active materials are highly dependent on the intrinsic properties of their constituents (fibers, molecular motors, and energy), which makes it difficult to control their behavior. Being able to manipulate directly the constitutive elements of the active gel could provide additional control parameters. Here, we report a strategy to functionalize and manipulate active microtubule-based structures upon magnetic actuation. We engineered protein nanocage ferritins as magnetic labels targeting molecular motors (Eg5 kinesin motors). We first mixed these magnetic motors with individual microtubules, allowing for their manipulation. In order to generate a magnetic-responsive gel, we then mixed the magnetic motors with active microtubule-based structures and characterized their dynamic behavior. We found that the magnetic forces applied on magnetic motors slowed down the dynamics of the microtubule structures as well as constrained their rotation. Our results highlight how genetically encoded magnetic elements, behaving as magnetic actuators, could perturb active gels.

USEAQ: Ultra-fast Superpixel Extraction via Adaptive Sampling from Quantized Regions.

We present a novel and highly efficient superpixel extraction method called USEAQ to generate regular and compact superpixels in an image. To reduce the computational cost of iterative optimization procedures adopted in most recent approaches, the proposed USEAQ for superpixel generation works in a one-pass fashion. It firstly performs joint spatial and color quantizations and groups pixels into regions. It then takes into account the variations between regions, and adaptively samples one or a few superpixel candidates for each region. It finally employs maximum a posteriori (MAP) estimation to assign pixels to the most spatially consistent and perceptually similar superpixels. It turns out that the proposed USEAQ is quite efficient, and the extracted superpixels can precisely adhere to boundaries of objects. Experimental results show that USEAQ achieves better or equivalent performance compared to the stateof- the-art superpixel extraction approaches in terms of boundary recall, undersegmentation error, achievable segmentation accuracy, the average miss rate, average undersegmentation error, and average unexplained variation, and it is significantly faster than these approaches.

Programmed Self-Assembly of a Biochemical and Magnetic Scaffold to Trigger and Manipulate Microtubule Structures.

Artificial bio-based scaffolds offer broad applications in bioinspired chemistry, nanomedicine, and material science. One current challenge is to understand how the programmed self-assembly of biomolecules at the nanometre level can dictate the emergence of new functional properties at the mesoscopic scale. Here we report a general approach to design genetically encoded protein-based scaffolds with modular biochemical and magnetic functions. By combining chemically induced dimerization strategies and biomineralisation, we engineered ferritin nanocages to nucleate and manipulate microtubule structures upon magnetic actuation. Triggering the self-assembly of engineered ferritins into micrometric scaffolds mimics the function of centrosomes, the microtubule organizing centres of cells, and provides unique magnetic and self-organizing properties. We anticipate that our approach could be transposed to control various biological processes and extend to broader applications in biotechnology or material chemistry.

iGC-an integrated analysis package of gene expression and copy number alteration.

BACKGROUND: With the advancement in high-throughput technologies, researchers can simultaneously investigate gene expression and copy number alteration (CNA) data from individual patients at a lower cost. Traditional analysis methods analyze each type of data individually and integrate their results using Venn diagrams. Challenges arise, however, when the results are irreproducible and inconsistent across multiple platforms. To address these issues, one possible approach is to concurrently analyze both gene expression profiling and CNAs in the same individual. RESULTS: We have developed an open-source R/Bioconductor package (iGC). Multiple input formats are supported and users can define their own criteria for identifying differentially expressed genes driven by CNAs. The analysis of two real microarray datasets demonstrated that the CNA-driven genes identified by the iGC package showed significantly higher Pearson correlation coefficients with their gene expression levels and copy numbers than those genes located in a genomic region with CNA. Compared with the Venn diagram approach, the iGC package showed better performance. CONCLUSION: The iGC package is effective and useful for identifying CNA-driven genes. By simultaneously considering both comparative genomic and transcriptomic data, it can provide better understanding of biological and medical questions. The iGC package's source code and manual are freely available at https://www.bioconductor.org/packages/release/bioc/html/iGC.html .

Development of a prediction model for radiosensitivity using the expression values of genes and long non-coding RNAs.

Radiotherapy has become a popular and standard approach for treating cancer patients because it greatly improves patient survival. However, some of the patients receiving radiotherapy suffer from adverse effects and do not obtain survival benefits. This may be attributed to the fact that most radiation treatment plans are designed based on cancer type, without consideration of each individual's radiosensitivity. A model for predicting radiosensitivity would help to address this issue. In this study, the expression levels of both genes and long non-coding RNAs (lncRNAs) were used to build such a prediction model. Analysis of variance and Tukey's honest significant difference tests (P < 0.001) were utilized in immortalized B cells (GSE26835) to identify differentially expressed genes and lncRNAs after irradiation. A total of 41 genes and lncRNAs associated with radiation exposure were revealed by a network analysis algorithm. To develop a predictive model for radiosensitivity, the expression profiles of NCI-60 cell lines along, with their radiation parameters, were analyzed. A genetic algorithm was proposed to identify 20 predictors, and the support vector machine algorithm was used to evaluate their prediction performance. The model was applied to 2 datasets of glioblastoma, The Cancer Genome Atlas and GSE16011, and significantly better survival was observed in patients with greater predicted radiosensitivity.

Improvement of clinical parameters in patients with gastroesophageal reflux disease after radiofrequency energy delivery.

AIM: To evaluate the efficacy of Stretta procedure with gastroesophageal reflux disease (GERD) based on symptom control, medication changes and oesophagitis grade. METHODS: Ninety patients with a history of GERD underwent Stretta procedure from June 2007 to March 2010. All patients with GERD diagnosed by the presence of endoscopically evidenced oesophagitis or abnormal esophageal pH testing. We evaluated GERD-health-related quality of life, satisfaction, medication use and endoscopy at baseline, 6, 12 mo after treatment. Complications of the procedure were analyzed. RESULTS: We found that patients experienced significant changes in symptoms of GERD after Stretta procedure. The onset of GERD symptom relief was less than 2 mo (70.0%) or 2 to 6 mo (16.7%). The mean GERD-HRQL score was 25.6 (baseline), 7.3 (6 mo, P < 0.01), and 8.1 (12 mo, P < 0.01).The mean heartburn score was 3.3 (baseline), and 1.2 (12 mo, P < 0.05). The percentage of patients with satisfactory GERD control improved from 31.1% at baseline to 86.7% after treatment, and patient satisfaction improved from 1.4 at baseline to 4.0 at 12 mo (P < 0.01). Medication usage decreased significantly from 100% of patients on proton pump inhibitors therapy at baseline to 76.7% of patients showing elimination of medications or only as needed use of antacids/H2-RA at 12 mo. An improvement in endoscopic grade of oesophagitis was seen in 33 of the 41 patients. All patients had either no erosions or only mild erosive disease (grade A) at 6 mo. CONCLUSION: The experience with Stretta procedure confirms that it is well tolerated, safe, effective and durable in the treatment of GERD. The Stretta procedure provides the drug-refractory patients with a new minimally invasive method.

[Pneumo-peritoneum helico-CT imaging in post-operative peritoneal adhesion].

OBJECTIVE: To discuss the diagnostic value of pneumoperitoneum helico-CT imaging (PHCT) in cases of post-operative peritoneal adhesion (POPA). METHODS: We retrospectively analyzed the PHCT scan pictures from 32 consecutive patients with chronic abdominal pain or recurrent mechanical intestinal obstruction after abdominal operation. RESULTS: In a normal peritoneal cavity without adhesion, an air distended dome-like space would be demonstrated with the abdominal organs arranged smoothly on the bottom of the shadow. Any additional shadow appearing in the dome-space would suggest adhesion or something abnormal. Positive findings of peritoneal adhesion were found in 30 of the 32 patients (93.75%). A spot adhesion at the abdominal wall making a kinking of intestine usually showed a cuneiform bulging shadow pointed to the roof of the dome-space. Organs involved in the adhesion may be single or multiple, including the liver, stomach, small intestine, colon, uterus, and omentum. In all the 32 patients, PHCT diagnosis was confirmed by the subsequent laparoscopy treatment. CONCLUSION: PHCT imaging is valuable in making a definite diagnosis of POPA, particularly before a blind laparoscopic exploration. It is a replacement for laparoscopy but much simpler, and may offer a valuable help in dealing with the difficult cases of suspected POPA. A negative imaging is sometimes very important to an undetermined postoperative chronic abdominal pain.

Irritable bowel syndrome: an international study of symptoms in eight countries.

OBJECTIVES: This report is a preliminary comparative study of irritable bowel syndrome symptoms in eight countries, USA, Mexico, Canada, England, Italy, Israel, India, and China. We also assessed global symptom patterns and correlations and relationships to several psychosocial variables. METHODS: Two hundred and thirty-nine participants completed a bowel symptom scale composed of four symptoms, abdominal pain or discomfort, bloating, diarrhea, and constipation as well as two psychosocial questionnaires, quality of relationship and attribution of symptoms to physical or emotional factors. RESULTS: Pain score in Italy, with the least urban population, was significantly higher than six of the seven other countries whereas it was lowest in India and England. Bloating was highest in Italy and constipation was highest in Mexico, both significantly higher than five other countries. Diarrhea was higher in China than five other countries. All significance values were P<0.05. Globally, diarrhea was less common than constipation, P<0.001 and bloating significantly correlated with constipation as well with pain, P<0.05. Composite analysis of psychosocial variables and symptoms indicated that family conflict correlated directly, P<0.05, whereas family support correlated indirectly, P<0.01, with pain and bloating. Pain, bloating and diarrhea were significantly attributed to physical etiology, P<0.01, whereas only diarrhea was attributed to emotional cause, P<0.05. CONCLUSION: This study suggests that there are significant variations in irritable bowel syndrome symptoms in different geographic locations around the world. Various hypotheses that may explain our data such as cultural beliefs, gut contamination, urban and rural location, dietary practice, and psychosocial factors should be further investigated.

[Evaluation of the quality of life of patients with irritable bowel syndrome].

OBJECTIVE: To explore and assess the health-related quality of life (HRQOL) of irritable bowel syndrome (IBS) patients in the population. METHODS: Random clustered sampling involving permanent inhabitants aged 18 - 80 yr was carried out under stratification of urban and suburban areas in Guangdong Province. Altogether 231 IBS patients fulfilling the Rome II criteria and 636 Non-IBS as control were collected. The impact of IBS on HRQOL was evaluated using the Chinese version of SF-36. RESULTS: (1) There were no statistically significant differences between IBS and Non-IBS groups in aspects of sex, age educational level, and distribution according to areas (P > 0.05). (2) IBS patients reported significantly poorer HRQOL than controls (Non-IBS) on all SF-36 subscales (P < 0.05). The patients had poorer HRQOL than the Non-patients, but their differences weren't significant (P > 0.05). (3) The scores on all SF-36 subscales were highly associated with the frequency of abdominal pain in IBS patients (P < 0.05); They were also correlated to degree of effects of IBS symptoms on life reported by IBS patients (P < 0.05); The association between the scores and the symptom of fatigue which is the most extra-intestinal symptom in IBS was significant (P < 0.05); (4) Copying style was highly correlated to the eight SF-36 subscales; IBS still had a significant impact on patients after partialing out the effect of copying style. CONCLUSIONS: IBS symptoms had a negative impact on HRQOL and the SF-36 could be adopted to detect the differences between IBS group and Non-IBS group, which may be used as an outcome measure in future treatment studies. However, the development of IBS-specific measures of quality of life is necessary.

[A population-based epidemiologic study of irritable bowel syndrome in Guangdong province].

OBJECTIVE: To explore the prevalence of irritable bowel syndrome (IBS) and its risk factors in Guangdong province. METHODS: A questionnaire was used to screen IBS by face-to-face interviews according to Manning (modified including symptoms of constipation) and Rome II criteria. Random clustered sampling involving permanent inhabitants aged 18 - 80 years was carried out under stratification of urban and suburban areas. Potential risk factors were explored by comparing the frequencies among IBS group and non-IBS group using chi(2) and logistic analysis of multivariate adjusted for age and gender. RESULTS: A total of 4178 residents (male 1907, female 2271) were investigated. Mean age among the responders was (43 +/- 14) years. The response rate was 98%. The adjusted prevalence of IBS in Guangdong province is 5.67% according to the modified Rome II criteria, and is 11.50% according to Manning criteria. There is no difference between urban and suburban areas. The female was predominant in IBS, and the ratio of male to female was 1:1.25 (Rome II) and 1:1.34 (Manning). The age was poorly correlated with the prevalence. Events including history of analgesic use such as NSAID (OR = 3.83), history of food allergies (OR = 2.68), psychological distress (OR = 2.18), life events (OR = 1.89), history of dysentery (OR = 1.63) and negative coping style (OR = 1.28) are highly associated with IBS (P < 0.05). CONCLUSION: IBS is a common disorder in Guangdong Province which deserves greater care and further investigation.

[Treatment of refractory irritable bowel syndrome with subclinical dosage of antidepressants].

OBJECTIVE: To investigate the effect of antidepressant on irritable bowel syndrome (IBS). METHODS: A self-control and follow-up study on subclinical dosage of antidepressants therapy (fluoxetine 10 mg/d, paroxetine 10 mg/d or doxepin 45 mg/d) for 9-12 wks in 46 patients with refractory IBS symptoms according to Rome II criteria was performed, the clinical outcomes were evaluated by scales changes of symptom-related-anxiety, severity index of symptom, and quality of life specific of IBS, as well as general psychiatric health by SCL-90 during treatment and follow-up periods. RESULTS: All 46 cases completed therapy and first follow-up unit (12 wks after treatment) (FFU), at the end of FFU, clinical symptoms in all patients were improved (P < 0.01). Comparison of the scores of symptom-related-anxiety, index of symptom, and quality of life specific of IBS at the end of FFU with that at basal level, indexes of the severity (3.4 +/- 1.5 vs 1.8 +/- 0.84) and frequency (3.8 +/- 1.60 vs 2.0 +/- 0.76) of symptoms were subsided significantly (P < 0.01, respectively); the scores of symptom-anxiety questionnaire including body anxiety (16.04 +/- 1.65 vs 10.83 +/- 1.64, P < 0.001), cognitive anxiety (18.78 +/- 2.12 vs 11.17 +/- 1.89, P < 0.001), fear (15.80 +/- 1.76 vs 10.78 +/- 1.85, P < 0.001) and avoiding (15.47 +/- 1.53 vs 10.16 +/- 1.59, P < 0.001) were also subsided significantly. In the meantime, IBS-QoL improved significantly (P < 0.05), dysphoria, body image, interference with activity, health worry, social reaction and overall scores were improved significantly (P < 0.01, respectively). The status of general psychiatric health was also improved significantly (P < 0.01). CONCLUSIONS: Treatment of refractory IBS with subclinical dosage antidepressant is rational and effective, However a further study on its mechanisms is suggested.