Optimization of Continuous Bioconversion Process of Glycerol to 1,3-Propanediol

This paper addresses the optimization of continuous bioconversion process of glycerol to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae. The studied bioprocess is a complex nonlinear system that involves the gene regulation for dha regulon, enzyme-catalytic kinetics on the reductive pathway, the active transport of glycerol and (passive) diffusion of 1,3-PD across the cell membrane, and the inhibition of glycerol dehydratase (GDHt) and 1,3-propanediol oxidoreductase (PDOR) by 3-hydroxypropionaldehy (3-HPA). We first propose a nonlinear optimization model that can maximize the production rate of 1,3-PD. Then the optimal solution of this optimization problem is obtained by using an interior point method. In this approach a sequence of barrier problems are solved iteratively. We finally obtain the maximum production rate of 1,3-PD increased more than 22.86 times its initial value

Serum lactate dehydrogenase activities as systems biomarkers for 48 types of human diseases

Most human diseases are systems diseases, and systems biomarkers are better fitted for diagnostic, prognostic, and treatment monitoring purposes. To search for systems biomarker candidates, lactate dehydrogenase (LDH), a housekeeping protein expressed in all living cells, was investigated. To this end, we analyzed the serum LDH activities from 172,933 patients with 48 clinically defined diseases and 9528 healthy individuals. Based on the median values, we found that 46 out of 48 diseases, leading by acute myocardial infarction, had significantly increased (p  0.8) for hepatic encephalopathy and lung fibrosis

Three-Dimensional Shape Measurements of Specular Objects Using Phase-Measuring Deflectometry

The fast development in the fields of integrated circuits, photovoltaics, the automobile industry, advanced manufacturing, and astronomy have led to the importance and necessity of quickly and accurately obtaining three-dimensional (3D) shape data of specular surfaces for quality control and function evaluation. Owing to the advantages of a large dynamic range, non-contact operation, full-field and fast acquisition, high accuracy, and automatic data processing, phase-measuring deflectometry (PMD, also called fringe reflection profilometry) has been widely studied and applied in many fields. Phase information coded in the reflected fringe patterns relates to the local slope and height of the measured specular objects. The 3D shape is obtained by integrating the local gradient data or directly calculating the depth data from the phase information. We present a review of the relevant techniques regarding classical PMD. The improved PMD technique is then used to measure specular objects having discontinuous and/or isolated surfaces. Some influential factors on the measured results are presented. The challenges and future research directions are discussed to further advance PMD techniques. Finally, the application fields of PMD are briefly introduce

A novel ZRS variant causes preaxial polydactyly type I by increased sonic hedgehog expression in the developing limb bud.

PurposePreaxial polydactyly (PPD) is a common congenital hand malformation classified into four subtypes (PPD I-IV). Variants in the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene are linked to most PPD types. However, the genes responsible for PPD I and the underlying mechanisms are unknown.MethodsA rare large four-generation family with isolated PPD I was subjected to genome-wide genotyping and sequence analysis. In vitro and in vivo functional studies were performed in Caco-2 cells, 293T cells, and a knockin transgenic mouse model.ResultsA novel g.101779T>A (reference sequence: NG_009240.2; position 446 of the ZRS) variant segregates with all PPD I-affected individuals. The knockin mouse with this ZRS variant exhibited PPD I phenotype accompanying ectopic and excess expression of Shh. We confirmed that HnRNP K can bind the ZRS and SHH promoters. The ZRS mutant enhanced the binding affinity for HnRNP K and upregulated SHH expression.ConclusionOur results identify the first PPD I disease-causing variant. The variant leading to PPD I may be associated with enhancing SHH expression mediated by HnRNP K. This study adds to the ZRS-associated syndromes classification system for PPD and clarifies the underlying molecular mechanisms

Enlarging the Stokes Shift by Weakening the π-Conjugation of Cyanines for High Signal-To-Noise Ratiometric Imaging

The signal-to-noise ratio (SNR) is one of the key features of a fluorescent probe and one that often defines its potential utility for in vivo labeling and analyte detection applications. Here, it is reported that introducing a pyridine group into traditional cyanine-7 dyes in an asymmetric manner provides a series of tunable NIR fluorescent dyes (Cy-Mu-7) characterized by enhanced Stokes shifts (≈230 nm) compared to the parent cyanine 7 dye (nm). The observed Stokes shift increase is ascribed to symmetry breaking of the Cy-Mu-7 core and a reduction in the extent of conjugation. The fluorescence signals of the Cy-Mu-7 dyes are enhanced upon confinement within the hydrophobic cavity of albumin or via spontaneous encapsulation within micelles in aqueous media. Utilizing the Cy-Mu-7, ultra-fast in vivo kidney labeling in mice is realized, and it is found that the liver injury will aggravate the burden of kidney by monitoring the fluorescence intensity ratio of kidney to liver. In addition, Cy-Mu-7 could be used as efficient chemiluminescence resonance energy transfer acceptor for the reaction between H O and bisoxalate. The potential utility of Cy-Mu-7 is illustrated via direct monitoring fluctuations in endogenous H O levels in a mouse model to mimic emergency room trauma

Effects of Forage Sources on Rumen Fermentation Characteristics, Performance, and Microbial Protein Synthesis in Midlactation Cows

Eight multiparous Holstein cows (632±12 kg BW; 135±16 DIM) were used in a replicated 4×4 Latin square design to evaluate the effects of forage sources on rumen fermentation characteristics, performance, and microbial protein (MCP) synthesis. The forage portion of the diets contained alfalfa hay (AH), oat hay (OH), Leymus chinensis (LC), or rice straw (RS) as the primary source of fiber. Diets were isonitrogenous and isocaloric, and cows were fed four corn silages based total mixed rations with equivalent nonfiber carbohydrate (NFC) and forage neutral detergent fiber (NDF). Dry matter intake was not affected by the source of dietary forages, ranging from 18.83 to 19.20 kg/d, consequently, milk yield was similar among diets. Because of the numerical differences in milk fat and milk protein concentrations, 4% FCM and ECM yields were unchanged (p>0.05). Mean rumen pH, NH3-N content, and concentrations of volatile fatty acids in the rumen fluid were not affected by the treatments (p>0.05). Dietary treatments did not affect the total tract apparent digestibility of dry matter, organic matter, and crude protein (p>0.05); however, digestibility of NDF and acid detergent fiber in RS diet was higher compared with AH, OH, and LC diets (p<0.05). Total purine derivative excretion was higher in cows fed AH, OH, and LC diets compared with those fed RS diet (p<0.05), consequently, estimated MCP synthesis was 124.35 g/d higher in cows fed AH diet compared with those fed RS diet (p<0.05). The results indicated that cows fed AH, OH, LC, and RS diets with an equivalent forage NDF and NFC have no unfavourable effect on the ruminal fermentation and productive parameters

Evaluation of Renal Tissue Oxygenation Using Blood Oxygen Level-Dependent Magnetic Resonance Imaging in Chronic Kidney Disease

Background: Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) has been widely used to assess renal oxygenation changes in different kidney diseases in recent years. This study was designed to evaluate and compare renal tissue oxygenation using 2 BOLD-MRI analysis methods, namely, the regional and whole-kidney region of interest (ROI) selection methods. Methods: The study ended up with 10 healthy controls and 40 chronic kidney disease (CKD) patients without dialysis. Their renal BOLD-MRI data were analyzed using whole-kidney ROI selection method and compared with regional ROI selection method. Results: We found the cortical, medullary, and whole-kidney R2* values were significantly higher in CKD patients than those in controls. Compared with the regional ROI selection method, the whole-kidney ROI selection method yielded higher cortical R2* values in both controls and CKD patients. The whole-kidney R2* values of deteriorating renal function group were significantly higher than those in stable renal function group. Conclusions: Cortical and medullary oxygenation was decreased significantly in CKD patients compared with the healthy controls, particularly in the medulla. The whole-kidney R2* values were positively correlated with kidney function and inversely correlated with the estimated glomerular filtration rate and effective renal plasma flow. Whole-Kidney R2* value might effectively predict the progression of renal function in patients with CKD

Role of Positive Selection in Functional Divergence of Mammalian Neuronal Apoptosis Inhibitor Proteins during Evolution

Neuronal apoptosis inhibitor proteins (NAIPs) are members of Nod-like receptor (NLR) protein family. Recent research demostrated that some NAIP genes were strongly associated with both innate immunity and many inflammatory diseases in humans. However, no similar phenomena have been reported in other mammals. Furthermore, some NAIP genes have undergone pseudogenization or have been lost during the evolution of some higher mammals. We therefore aimed to determine if functional divergence had occurred, and if natural selection had played an important role in the evolution of these genes. The results showed that NAIP genes have undergone pseudogenization and functional divergence, driven by positive selection. Positive selection has also influenced NAIP protein structure, resulting in further functional divergence