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Emergent genetic oscillations in a synthetic microbial consortium
Chen, Ye,Kim, Jae Kyoung,Hirning, Andrew J.,Josić,, Kreš,imir,Bennett, Matthew R. American Association for the Advancement of Scienc 2015 Science Vol.349 No.6251
<P><B>Engineering cell population behavior</B></P><P>Attaining the full promise of synthetic biology will require designing population-level behaviors of multiple interacting cell types. As a start, Chen et al. engineered two strains of the bacterium <I>Escherichia coli</I> to produce signaling molecules that regulate transcription in the complementary strain (see the Perspective by Teague and Weiss). The signaling circuit was successfully designed to produce feedback loops that produce synchronous oscillations in transcription between the two strains. A mathematical model helped determine how to modulate the oscillations and control their robustness to perturbations.</P><P><I>Science</I>, this issue p. 986; see also p. 924</P><P>A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types—an “activator” strain and a “repressor” strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types.</P>
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Chen Ziming,Li Mengyuan,Chen Peilin,Tai Andrew,Li Jiayue,Bassonga Euphemie Landao,Gao Junjie,Liu Delin,Wood David,Kennedy Brendan F.,Zheng Qiujian,Zheng Ming H. 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-
Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy. We simulated the disease condition by imposing a 9% strain overload on three-dimensional mouse tendon constructs in our cyclic uniaxial stretching bioreactor. The three-dimensional mouse tendon constructs under normal loading with 6% strain exhibited an extended mitochondrial network, as observed through live-cell confocal laser scanning microscopy. In contrast, mechanical overload led to a fragmented mitochondrial network. Our microscopic and immunoblot results demonstrated that mechanical loading induced tendon cells to release ExtraMito particles. Furthermore, we showed that mEPs released from tendon cells overloaded with a 9% strain (mEP9%) induced macrophage chemotaxis and increased the production of proinflammatory cytokines, including IL-6, CXCL1, and IL-18, from macrophages compared to mEP0%, mEP3%, and mEP6%. Partial depletion of the ExtraMito particles from mEP9% by magnetic-activated cell sorting significantly reduced macrophage chemotaxis. N-acetyl-L-cysteine treatment preserved the mitochondrial network in overloaded tendon cells, diminishing overload-induced macrophage chemotaxis toward mEP9%. These findings revealed a novel mechanism of tendinopathy; in an overloaded environment, ExtraMito particles convey mechanical response signals from tendon cells to the immune microenvironment, culminating in tendinopathy.
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Chen, Season S.,Wang, Lei,Yu, Iris K.M.,Tsang, Daniel C.W.,Hunt, Andrew J.,Jé,rô,me, Franç,ois,Zhang, Shicheng,Ok, Yong Sik,Poon, Chi Sun Elsevier 2018 Bioresource technology Vol.247 No.-
<P><B>Abstract</B></P> <P>This study aims to produce levulinic acid (LA) from paper towel waste in environment-friendly and economically feasible conditions, and evaluate the difference using solid and aqueous Brønsted acids. Direct dehydration of glucose to LA required sufficiently strong Brønsted acidity, where Amberlyst 36 demonstrated rapid production of approximately 30Cmol% of LA in 20min. However, the maximum yield of LA was limited by mass transfer. In contrast, the yield of LA gradually increased to over 40Cmol% in 1M H<SUB>2</SUB>SO<SUB>4</SUB> at 150°C in 60min. The SEM images revealed the conversion in dilute acids under microwave at 150°C resulting in swelling structures of cellulose, which were similar to the pre-treatment process with concentrated acids. Further increase in reaction temperature to 200°C significantly shortened the reaction time from 60 to 2.5min, which saved the energy cost as revealed in preliminary cost analysis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 30% of levulinic acid (LA) yielded from paper towel over Amberlyst 36 in 20min. </LI> <LI> Maximum yield of LA was comparable using dilute sulphuric acid at 150 and 200°C. </LI> <LI> Cellulose underwent swelling in dilute acid with microwave heating at 150°C. </LI> <LI> Conversion at 200°C shortened reaction time and reduced total energy consumption. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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PROBABILITY DISTRIBUTION OF CADMIUM PARTITIONING COEFFICIENTS OF CROPLAND SOILS
Chen, Weiping,Chang, Andrew C.,Wu, Laosheng,Li, Lianqing,Kwon, Soon-Ik,Page, Albert L. Williams & Wilkins Co 2007 Soil science Vol.172 No.2
The solution to solid partitioning coefficient (Kd) is an important parameter in assessing the environmental and health risks of potentially toxic metals in soils. Ideally, the metal in solution phase should be determined at the field moisture condition under which the exposures take place. In reality, it is often represented by the concentration in extracts of a given soil-to-water ratio. Using cadmium (Cd) as an example, we demonstrated the uncertainties in determining the soil solution concentrations in cropland soils where the metal contents are only slightly higher than the baselines. Results of extraction experiments showed the Cd concentration of soil solution under simulated field moisture conditions (i.e., water-to-soil ratio of 0.5) tends to be stochastic and follows a normal distribution. The distribution of Kd of two California cropland soils was quantitatively described by a normal probability distribution function. The normal distribution pattern wasfurther validated by data collected in the field. When Kd is characterized in the probabilistic terms, the risks of environmental andhealth harm of metals in the cropland soils may be more appropriately assessed.
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Management of failed UKA to TKA: conventional versus robotic-assisted conversion technique
Yun Andrew G.,Qutami Marilena,Chen Chang-Hwa Mary,Pasko Kory B. Dylan 대한슬관절학회 2020 대한슬관절학회지 Vol.32 No.-
Background: Failure of unicompartmental knee arthroplasty (UKA) is a distressing and technically challenging complication. Conventional conversion techniques (CCT) with rods and jigs have produced varying results. A robotic-assisted conversion technique (RCT) is an unexplored, though possibly advantageous, alternative. We compare our reconstructive outcomes between conventional and robotic methods in the management of failed UKA. Methods: Thirty-four patients with a failed UKA were retrospectively reviewed. Patients underwent conversion total knee arthroplasty (TKA) with either a CCT or RCT. Seventeen patients were included in each group. All procedures were done by a single surgeon at a single institution, with a mean time to follow-up of 3.6 years (range, 1 to 12). The primary outcome measures were the need for augments and polyethylene thickness. Secondary outcome measures were complications, need for revision, estimated blood loss (EBL), length of stay, and operative time. Results: The mean polyethylene thickness was 12mm (range, 9 to 15) in the CCT group and 10mm (range, 9 to 14) in the RCT groups, with no statistical difference between the two groups (P = 0.07). A statistically significant difference, however, was present in the use of augments. In the CCT group, five out of 17 knees required augments, whereas none of the 17 knees in the RCT group required augments (P = 0.04). Procedurally, roboticassisted surgery progressed uneventfully, even with metal artifact noted on the preoperative computerized tomography (CT) scans. Computer mapping of the residual bone surface after implant removal was a helpful guide in minimizing resection depth. No further revisions or reoperations were performed in either group. Conclusions: Robotic-assisted conversion TKA is technically feasible and potentially advantageous. In the absence of normal anatomic landmarks to guide conventional methods, the preoperative CT scans were unexpectedly helpful in establishing mechanical alignment and resection depth. In this limited series, RCT does not seem to be inferior to CCT. Further investigation of outcomes is warranted.
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Xiaomei Chen,Andrew Longstaff,Simon Parkinson,Alan Myers 한국정밀공학회 2014 International Journal of Precision Engineering and Vol. No.
This paper presents an evaluation method for the rapid and automatic detection of position errors of arrays of small holes on complex-curved and freeform surfaces that can satisfy the special demands of the aviation and automobile industries. The evaluation is based on the dual-sensor autofocusing method. The dual-sensor unit is the combination of a tactile probe and an optical vision sensor. The tactile probe detects the focal position for the optical vision sensor by probing the distance between the objective lens of the microscope and the location of each small hole. The optical vision sensor focuses to this position for capturing the image of the artifact under inspection. As a case study, a pattern of φ 0.5 mm small holes centripetally drilled with equal-angular distribution on the circumference of an elliptical cylinder shell is investigated. The autofocusing errors caused by the radius of the tactile probe and the position errors of the small holes are evaluated mathematically. Subsequently, a standalone dual-sensor autofocusing unit is built and integrated into a user-controllable 3D coordinate test rig. It is used to autofocus and capture the images of small holes. The centroid positions and deviations of the holes are automatically and rapidly detected from the captured images.
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( Ira Jacobson ),( Andrew J. Muir ),( Eric Lawitz ),( Edward Gane ),( Brian Conway ),( Peter J. Ruane ),( Ziad Younes ),( Frances Chen ),( Marianne Camargo ),( Anand P. Chokkalingam ),( C. Stephen Dje 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: In patients with HCV cirrhosis, a sustained virologic response (SVR) is associated with improved clinical outcomes; however, the temporal course of changes in fibrosis is poorly understood. Our aim was to evaluate changes in noninvasive tests of fibrosis (NITs) in this setting to gain insights into the natural history of cirrhosis regression following removal of the causative exposure. Methods: We studied patients with HCV cirrhosis who achieved SVR with sofosbuvir (SOF)-based regimens (in a trial or clinical practice) in an ongoing, prospective cirrhosis registry (NCT02292706). Patients underwent routine clinical and laboratory assessments, including semi-annual Child-Pugh-Turcotte (CPT) scoring and measurement of the Enhanced Liver Fibrosis (ELF) test, as well as annual liver stiffness measurement by transient elastography (LS by TE). Changes in fibrosis were estimated based on ELF response (defined as ≥0.5 unit reduction), and shifts in estimated fibrosis categories based on ELF (F3, ELF 9.8-11.3; F4, ELF >11.3) and LS by TE (F3, 9.6-12.5 kPa; F4, >12.5 kPa). Logistic regression was used to identify predictors of fibrosis improvement as defined by NITs. Results: 1,574 subjects with HCV cirrhosis (32% female, 39% BMI ≥30 kg/㎡, 7% CPT class B/C) were included in this study; median interval between SVR and registry enrollment was 38 weeks (IQR 27-60). At enrollment, median (IQR) ELF was 14.3 (9.5, 22.1); 586 (37%) and 247 (16%) patients had ELF scores consistent with F3 and F4 fibrosis, respectively. Median LS by TE was 9.9 kPa (9.2, 10.8); 761 (57%) and 227 (17%) patients had LS consistent with F3 and F4 fibrosis, respectively. As of May 2019, median duration of follow-up after registry enrollment was 123 weeks (IQR 96, 168). At week 144, 49% of those with baseline CPT class B/C had improved CPT class, while 98% of those with baseline CPT class A remained in CPT class A. During follow-up, changes in ELF and LS by TE suggested fibrosis improvement in an increasing proportion of patients with both F3 and F4 fibrosis at enrollment (Figure 1). ELF score improved by >0.5 units at week 144 in 27% and 47% of patients with baseline F3 and F4 fibrosis, respectively. Predictors of ELF improvement included higher ELF (P<0.001) and AST (P=0.049), and lower platelets (P=0.02) and BMI (P=0.10) at registry baseline. Conclusions: In patients with cirrhosis in whom HCV has been eradicated by SOF-based therapy, NITs suggest significant fibrosis improvement in 25-50% of patients within 3 years. Associations between reductions in these NITs and improvements in clinical outcomes require evaluation during longer-term follow-up.
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