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A major challenge in bacterial developmental biology has been to understand the mechanisms underlying cell fate decisions. Some differentiated cell types display cooperative behaviour. Cooperation is one of the greatest mysteries of evolutionary biology and microbes have been considered as an excellent system for experimentally testing evolution theories. Bacillus thuringiensis (Bt) is a spore-forming bacterium, which is genetically closely related to B. anthracis, the agent of anthrax, and to B. cereus, an opportunistic human pathogen. The defining feature that distinguishes Bt from its relatives is its ability to produce crystal inclusions in the sporulating cells. These toxins are solubilized after ingestion and are cooperative public goods in insect hosts. In this study, we describe a Bt strain LM1212 that presents the unique ability to terminally differentiate into crystal producers and spore formers. Transcriptional analysis based on lacZ and gfp reporter genes suggested that this phenotype is the consequence of a new type of cell differentiation associated with a novel regulation mode of cry gene expression. The differentiating crystal-producer phenotype has higher spore productivity than a typical Bt strain and is better able to compete with Cry toxin null 'cheaters'. Potentially, this division of labour provides additional fitness benefits in terms of spore viability or durability of Cry toxin. [ABSTRACT FROM AUTHOR]

Aims To facilitate future applications of transgenic or knockout technologies in studies of simulated birth trauma induced stress urinary incontinence (SUI), we aimed to create a mouse model of SUI and explore the possible pathogenesis of this condition. Methods Thirty female C57BL/6 mice were randomly distributed into five groups. Four groups underwent vaginal distention (VD) for 1 hr, using a modified 6-Fr. Foley catheter with a balloon dilated to 0.3, 0.2, or 0.1 ml or sham distention. Four days after VD, all mice underwent leak-point pressure (LPP) measurement via an implanted suprapubic tube (SPT). The normal control group only had SPT placement and LPP measurement. After sacrifice, the urethras of the mice were harvested for routine histological examination and nerve staining. Results LPPs were significantly lower in groups after VD with 0.3- or 0.2-ml balloon than in control and sham distention groups (10.29 ± 6.70, 14.65 ± 6.51, 37.78 ± 5.10, and 30.30 ± 5.30 cm H2O, respectively). There were no significant differences in LPP between control and sham groups. Histology showed no significant differences in urethral striated muscle among the five groups. The density of immunoreactive neurofilaments in the urethra decreased after VD with 0.3- or 0.2-ml balloon. Conclusion As a model of birth trauma, VD can induce SUI in female mice, the severity of which is related to intravaginal balloon size. Partial urethral denervation plays a plausible role in the pathogenesis of SUI. This novel mouse model could be used for further mechanistic studies of female SUI. Neurourol. Urodynam. 27:353-358, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesized that transection of the pubo-urethral ligament in the female rat would cause stress urinary incontinence, as indicated by decreased leak point pressure. We created a novel model of pubo-urethral ligament deficiency in the rat and validated our model through comparison with an established model of stress urinary incontinence. Materials and Methods: A total of 21 female age matched Sprague-Dawley rats (Harlan, Indianapolis, Indiana) were randomly assigned to 5 groups, including pubo-urethral ligament transection or sham pubo-urethral ligament transection with leak point pressure measured 4 days (groups 1 and 2) or 10 days (groups 3 and 4) postoperatively and bilateral pudendal nerve transection with leak point pressure measured 4 days postoperatively (group 5). Leak point pressure was measured in all groups via a suprapubic catheter. The Wilcoxon signed rank test was used to evaluate differences between the groups. Results: Leak point pressure was significantly decreased in the pubo-urethral ligament transection groups compared to that in the sham treated groups after 4 days (mean ± SEM 16.3 cm ±2.74 vs 36.6 ± 8.39 cm H2O, p <0.00001), although it was no different from that in the pudendal nerve transection group (14.5 ± 1.06 cm H2O, p <0.44). Ten days after surgery leak point pressure remained significantly lower in the pubo-urethral ligament transection groups compared to that in the sham treated groups (17.6 ± 6.36 vs 31.2 ± 5.14 cm H2O, p <0.00001), indicating the durability of pubo-urethral ligament transection for inducing stress urinary incontinence in female rats. Conclusions: Our results demonstrate that deficiency of the pubo-urethral ligament in the female rat induces stress urinary incontinence comparable to that in a previously established model of pudendal nerve transection induced stress urinary incontinence. This novel rat model could be used to investigate the mechanisms of urethral hypermobility in female stress urinary incontinence or potential therapeutic interventions for stress urinary incontinence. [Copyright &y& Elsevier]

The natural history of diabetes mellitus-induced remodeling of the urinary bladder is poorly understood. In this study, we examined temporal remodeling of the bladder in diabetic and diuretic rats. Male Sprague-Dawley rats were divided into three groups: streptozotocin-induced diabetic, 5% sucrose-induced diuretic, and age-matched control. Micturition and morphometric characteristics were evaluated using metabolic cages and light-microscopic examination of the bladder 4 days and 1, 2, 3, and 9 wk after induction. Digital image analysis was used to quantify equatorial cross-sectional areas of bladder tissue and lumen, as well as relative content of the three primary tissue components: smooth muscle, urothelium, and collagen. Diabetes and diuresis caused significant increases in fluid intake, urine output, and bladder weight. In both groups, progressive increases were observed in lumen area from 4 days to 3 wk after induction and in wall area from 2 to 3 wk after induction. Wall thickness decreased within the first 2 wk in the diabetic and diuretic rats but returned to control at 3 and 9 wk. As a percentage of total cross-sectional area, smooth muscle area increased, urothelium area was unchanged, and collagen area decreased in diabetic and diuretic rats after 2-3 wk compared with control rats. In conclusion, diabetes and diuresis induced similar bladder remodeling. Diabetes-induced diuresis caused adaptive physical changes in rat bladder by 4 days after induction; remodeling was observed by 2-3 wk after induction and remained stable from 3 to 9 wk. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic bladder dysfunction is among the most common and bothersome complications of diabetes mellitus. While bladder filling and voiding problems have been reported, the precise functional changes in diabetic bladders remain unclear. We investigated time dependent changes in bladder function in streptozotocin induced diabetic rats. Materials and Methods: Cystometrograms and detrusor muscle contractility were examined in male age matched control and diabetic Sprague-Dawley rats (Harlan, Indianapolis, Indiana) 3, 6, 9, 12 and 20 weeks after diabetes induction with streptozotocin. Results: Diabetes decreased average body weight and increased bladder weight, capacity and compliance. Peak detrusor leak pressure increased gradually from weeks 3 to 6 to 9 in diabetic rats (mean ± SEM 47.3 ± 2.5, 50.8 ± 3.0 and 56.0 ± 3.6 cm H2O) and in controls (36.9 ± 1.4, 37.7 ± 1.5 and 41.6 ± 1.81 cm H2O, respectively). However, at 12 and 20 weeks diabetic rats deviated strongly from this trend with peak detrusor leak pressure decreasing vs controls (41.6 ± 2.8 and 37.3 ± 0.9 vs 45.2 ± 1.7 and 49.6 ± 1.4 cm H2O, respectively) and post-void resting pressures increasing from 9-week levels vs controls (interactions p <0.0001). In contractility studies increased contractile force responses of diabetic animals to carbamylcholine chloride, potassium chloride, adenosine 5′-triphosphate and electric field stimulation peaked at 6 or 9 weeks but at 12 to 20 weeks they generally reverted toward those of controls (carbamylcholine chloride and electrical field stimulation interactions p = 0.0022 and 0.01, respectively). Conclusions: Diabetic bladders may undergo a transition from a compensated to a decompensated state and transition in the streptozotocin rat model may begin 9 to 12 weeks after induction. [Copyright &y& Elsevier]

Discusses the role of endogenous carbon monoxide (CO) in hypoxia. Measurement of CO levels in plasma, liver and kidney of rats; Occurrence of hemodynamic changes in accordance with the changes of CO; Statistical data related to changes of hemodynamic and blood gas.

The article "High‑depth resequencing of 312 accessions reveals the local adaptation of foxtail millet" written by Jianhua Wei et al was originally published electronically on the publisher's internet portal (currently Springerlink) [ABSTRACT FROM AUTHOR]

The inhibitory effects of delphinidin‐3‐O‐galactoside (DG) on the activities of tyrosinase (EC 1.14.18.1) (TY) from the edible Agaricus bisporus mushroom were investigated by enzyme kinetics, multispectroscopic methods, and molecular docking. As a result, DG showed strong inhibition on TY with the IC50 of 34.14 × 10–6 mol L–1. The inhibition mode of DG against TY was mixed type with α values of 5.09. The binding constant Ka and related thermodynamic parameters at the three different temperatures showed that the fluorescence quenching of TY by DG was static quenching. Synchronous fluorescence, three‐dimensional fluorescence, ultraviolet–visible spectroscopy, and circular dichroism spectroscopies confirmed that the conformation or microenvironment of the TY protein were changed after binding with DG. Molecular docking revealed that DG had strong binding affinity to TY through hydrogen bonding and van der Waals force, and the results were consistent with the fluorescence data. Our findings suggested that DG may be potential TY inhibitor. [ABSTRACT FROM AUTHOR]

Diabetes induces time-dependent alterations in urinary bladders. Long-term diabetes causes an underactive bladder. However, the fundamental mechanisms are still elusive. This study aimed to examine the histological changes and the potential molecular pathways affected by long-term diabetes in the rat bladder. Diabetes was induced in 8-week-old male Lewis rats by streptozotocin, while age-matched control rats received citrate buffer only. Forty-four weeks after diabetes induction, bladders were harvested for histological and molecular analyses. The expressions of proteins related to fibrosis, apoptosis and oxidative stress as well as the cellular signaling pathway in the bladder were examined by immunoblotting. Histological examinations illustrated diabetes caused detrusor hypertrophy and fibrotic changes in the bladder. Immunoblotting analysis demonstrated higher collagen I but lower elastin expression in the bladder in diabetic rats. These were accompanied by an increase in the expression of transforming growth factor-beta1, along with the downregulation of matrix metalloptoteinase-1, and upregulation of tissue inhibitor of metalloproteinase-1. Diabetic rats showed an increase in nitrotyrosine, but decrease in nuclear factor erythroid-related factor 2 (Nrf2) levels in the bladder. Enhanced apoptotic signaling was observed, characterized by increased expression of Bcl-2-associated X protein (Bax), decreased expression of Bcl-2, in the diabetic bladder. The nerve growth factor level was decreased in the diabetic bladder. A significant suppression in the protein expressions of phosphorylated extracellular signal-regulated kinases 1/2 was found in diabetic bladders. This study demonstrated that long-term diabetes caused molecular changes that could promote fibrosis and apoptosis in the bladder. Oxidative stress may be involved in this context. • Long-term diabetes causes detrusor hypertrophy and fibrotic changes in bladder. • Long-term diabetes leads to imbalances between MMP-1 and TIMP-1 in bladder. • Enhanced apoptotic signaling was observed in diabetic bladder. • Reduction of NGF and phosphorylated ERK1/2 was found in diabetic bladder. • Oxidative stress may be the central mediator of the above pathological changes. [ABSTRACT FROM AUTHOR]

In this study, an accurate and reliable method of ultra‐performance liquid chromatography coupled with a triple‐quadrupole tandem mass spectrometry was firstly developed and fully validated for the simultaneous determination of epicatechin, neoastilbin, astilbin, isoastilbin, engeletin and resveratrol in rat plasma after administration of Smilacis glabrae Roxb. extract. Naringenin was used as an internal standard (IS). The analyte and IS were separated on a C18 column by gradient elution with a mobile phase of acetonitrile–0.3% acetic acid at a flow rate of 0.25 mL/min for a total run time of 8 min. The method was validated in terms of selectivity, linearity, precision, accuracy, extraction recovery, matrix effect and stability. The developed method was successfully applied to determine the main pharmacokinetic parameters of six components in rat plasma. [ABSTRACT FROM AUTHOR]

A complete and accurate genome sequence provides a fundamental tool for functional genomics and DNA-informed breeding. Here, we assemble a high-quality genome (contig N50 of 6.99 Mb) of the apple anther-derived homozygous line HFTH1, including 22 telomere sequences, using a combination of PacBio single-molecule real-time (SMRT) sequencing, chromosome conformation capture (Hi-C) sequencing, and optical mapping. In comparison to the Golden Delicious reference genome, we identify 18,047 deletions, 12,101 insertions and 14 large inversions. We reveal that these extensive genomic variations are largely attributable to activity of transposable elements. Interestingly, we find that a long terminal repeat (LTR) retrotransposon insertion upstream of MdMYB1, a core transcriptional activator of anthocyanin biosynthesis, is associated with red-skinned phenotype. This finding provides insights into the molecular mechanisms underlying red fruit coloration, and highlights the utility of this high-quality genome assembly in deciphering agriculturally important trait in apple. Existing apple genome assemblies all derive from Golden Delicious. Here, the authors combine different sequencing technologies to assemble a high quality genome of an anther-derived homozygous genotype HFTH1 and find the association of a retrotransposon and red fruit colour. [ABSTRACT FROM AUTHOR]

Paecilomyces hepiali, belonging to the Eurotiales order Ascomycota, is an endoparasitic fungus that commonly exists in the naturalCordyceps sinensisanamorph stage. Here, we report the complete mitochondrial DNA sequences ofP. hepialifor the first time. The genome is 24,245 bp in length, encoding 15 protein-coding genes (PCGs), 2 rRNA genes, 25 tRNA genes and 3 homing endonucleases. The overall AT composition is 73.37% and the average AT content of PCG, rRNA, tRNA and non-coding region are 74.21%, 66.07%, 62.83% and 75.96%, respectively. Phylogenetic analysis with eight Ascomycota species and thirteen Basidiomycota species revealed thatP. hepialiis was more closely related toCordyceps bassiana, Cordycep smilitarisandCordyceps brongniartii. It is confirmed thatP. hepialiis a derivative ofCordyceps sinensis. This study provided valuable information on the gene contents of the mitochondrial genome and would facilitate the study of function and evolution ofP. hepiali. [ABSTRACT FROM AUTHOR]

In this work, two methods were proposed to improve the bonding quality of Ag sinter joining on Au surface finished substrate (Ag Au joint). The first method was preheating treatment to Au surface finished substrate before sintering. The second method proposed was increasing the initial thickness of the Au layer on the substrate. The bonding strength of the sintered specimen improved from 13.8 MPa to 25.4 MPa by a 250 °C substrate preheating treatment. Also, bonding strength increased from 13.3 MPa to 24.4 MPa as the initial thickness of Au layer was increased from 0.1 to 0.8 μm. SEM, EDS and XRD characterizations were conducted to analyze improvement of bonding strength, diffusion behavior between Au and Ag, and structure of Au layer. The results indicated that the enhancement of bonding strength was attributed to the increase of Au grain-size because larger Au grains can alleviate grain boundary diffusion that can diminish bonding strength. As a result of this finding, an empirical equation that indicates the correlation between bonding strength and Au grain-size was also proposed. • Ag sinter joining was conducted on the Au surface finished substrate. • Two methods were proposed for increasing the bonding strength of Ag Au joint. • Different diffusion processes were found on the original and preheated substrate. • Bonding strength of Ag Au joint is increased with the grain-size of Au surface finish. [ABSTRACT FROM AUTHOR]

Purpose: Diabetes mellitus, a metabolic disorder caused by an absolute or relative deficiency of insulin, is a debilitating and costly disease with multiple serious complications. Lower urinary tract complications are among the most common complications of diabetes mellitus. The most common, bothersome lower urinary tract complication of diabetes mellitus is diabetic cystopathy or diabetic bladder dysfunction. We reviewed the current translational knowledge of diabetic bladder dysfunction. Materials and Methods: We performed a search of the English literature through PubMed®. The key words used were diabetes and bladder dysfunction or cystopathy. Our data and perspective are provided for consideration of the future direction of research. Results: Despite traditional recognition of diabetic bladder dysfunction as a voiding problem characterized by poor emptying and overflow incontinence, recent clinical and experimental evidence indicate storage problems such as urgency and urge incontinence in diabetes mellitus cases. Recent experimental evidence from studies of diabetic bladder dysfunction in small animal models of diabetes mellitus show a temporal effect on diabetic bladder dysfunction. Early phase diabetes mellitus causes compensated bladder function and the late phase causes decompensated bladder function. The temporal theory could plausibly provide the scientific road map to correlate clinical and experimental findings, and identify the role of mechanisms such as polyuria, hyperglycemia, oxidative stress, autonomic neuropathy and decompensation of the bladder contractile apparatus in the creation of clinical and experimental manifestations of diabetic bladder dysfunction. Conclusions: Diabetic bladder dysfunction includes time dependent manifestations of storage and emptying problems. Identifying mechanistic pathways would lead to the identification of therapeutic intervention. [Copyright &y& Elsevier]

Purpose: Diabetes mellitus is a group of debilitating and costly diseases with multiple serious complications. Lower urinary tract complications or diabetic uropathy are among the most common complications of diabetes mellitus, surpassing widely recognized complications such as neuropathy and nephropathy. Diabetic uropathy develops in individuals with types 1 and 2 diabetes, and little is known about the natural history of these common and troublesome complications. Animal models have the potential to reveal mechanisms and aid in the development of treatment strategies. Materials and Methods: We present a review of available animal models of diabetes mellitus relative to their use in the study of diabetic uropathy. Results: Large and small animal models of diabetes mellitus are available. While large animals such as dogs and swine may closely mirror the human disease in size and phenotype, the time between diabetic complication onset and development, and associated husbandry expenditures can make acquiring data on statistically valid sample sizes prohibitively expensive. In contrast, small animal models (rats and mice) have much lower expenditures for a larger number of animals and compressed observation time due to a shorter life span. Also, mice are readily manipulated genetically to facilitate the isolation of the effect of single genes (transgenic and knockout mice). Type 1 diabetes mellitus can be induced chemically with streptozotocin, which is selectively toxic to pancreatic β cells. Type 2 diabetes mellitus models have been developed by selective breeding for hyperglycemia with or without associated obesity. Diabetic uropathy has been noted in several well characterized, predictable animal models of diabetes mellitus. Conclusions: Diabetic uropathy, including diabetic bladder dysfunction, has been more frequently studied in small animals with type I diabetes. The recent availability of transgenic models provides a new opportunity for further studies of diabetic uropathy in mouse models of types I and II diabetes mellitus. [Copyright &y& Elsevier]

Background: Interspecific postzygotic reproduction isolation results from large genetic divergence between the subgenomes of established hybrids. Polyploidization immediately after hybridization may reset patterns of homologous chromosome pairing and ameliorate deleterious genomic incompatibility between the subgenomes of distinct parental species in plants and animals. However, the observation that polyploidy is less common in vertebrates raises the question of which factors restrict its emergence. Here, we perform analyses of the genome, epigenome, and gene expression in the nascent allotetraploid lineage (2.95 Gb) derived from the intergeneric hybridization of female goldfish (Carassius auratus, 1.49 Gb) and male common carp (Cyprinus carpio, 1.42 Gb), to shed light on the changes leading to the stabilization of hybrids. Results: We firstly identify the two subgenomes derived from the parental lineages of goldfish and common carp. We find variable unequal homoeologous recombination in somatic and germ cells of the intergeneric F1 and allotetraploid (F22 and F24) populations, reflecting high plasticity between the subgenomes, and rapidly varying copy numbers between the homoeolog genes. We also find dynamic changes in transposable elements accompanied by genome merger and duplication in the allotetraploid lineage. Finally, we observe the gradual decreases in cis-regulatory effects and increases in trans-regulatory effects along with the allotetraploidization, which contribute to increases in the symmetrical homoeologous expression in different tissues and developmental stages, especially in early embryogenesis. Conclusions: Our results reveal a series of changes in transposable elements, unequal homoeologous recombination, cis- and trans-regulations (e.g. DNA methylation), and homoeologous expression, suggesting their potential roles in mediating adaptive stabilization of regulatory systems of the nascent allotetraploid lineage. The symmetrical subgenomes and homoeologous expression provide a novel way of balancing genetic incompatibilities, providing a new insight into the early stages of allopolyploidization in vertebrate evolution. [ABSTRACT FROM AUTHOR]

Background: Antibiotics and antibiotic resistance genes (ARGs) used in intensive animal farming threaten human health worldwide; however, the common resistome, ARG mobility, and ARG host composition in different animal manures and mixed manure composts remain unclear. In the present study, metagenomic assembly and cross-sample mapping were used to comprehensively decipher the common resistome and its potential mobility and hosts in animal manure and composts. Results: In total, 201 ARGs were shared among different animal (layer, broiler, swine, beef cow, and dairy cow) manures and accounted for 86–99% of total relative abundance of ARGs. Except for multidrug, sulfonamide, and trimethoprim resistance genes, the relative abundance of most ARGs in composts was significantly lower than that in animal manure. Procrustes analysis indicated that antibiotic residues positively correlated with ARG composition in manure but not in composts. More than 75% ARG subtypes were shared between plasmids and chromosomes in our samples. Transposases could play a pivotal role in mediating the transfer of ARGs between different phyla in animal manure and composting. Cross-sample mapping to contigs carrying ARGs showed that the hosts of common resistome in manure had preference on animal species, and the dominant genus of ARG host shifted from Enterococcus in manure to Pseudomonas in composts. The broad host range and linking with diverse mobile genetic elements (MGEs) were two key factors for ARGs, such as sul1 and aadA, which could survive during composting. The multidrug resistance genes represented the dominant ARGs in pathogenic antibiotic-resistant bacteria in manure but could be effectively controlled by composting. Conclusions: Our experiments revealed the common resistome in animal manure, classified and relative quantified the ARG hosts, and assessed the mobility of ARGs. Composting can mitigate ARGs in animal manure by altering the bacterial hosts; however, persistent ARGs can escape from the removal because of diverse host range and MGEs. Our findings provide an overall background for source tracking, risk assessment, and control of livestock ARGs. [ABSTRACT FROM AUTHOR]

The interaction mechanism of pelargonidin (PG) with tyrosinase was investigated by multi‐spectroscopy and molecular docking. As a result, PG had strong inhibitory activity on tyrosinase with the IC50 value of 41.94 × 10−6 mol·L−1. The inhibition type of PG against tyrosinase was determined as a mixed‐mode. Meanwhile, the fluorescence of tyrosinase was quenched statically by PG, and accompanied by non‐radiative energy transfer. The three‐dimensional (3‐D) fluorescence, ultraviolet‐visible spectroscopy (UV‐Vis) and circular dichroism spectroscopies (CD) indicated that PG decreased the hydrophobicity of the micro‐environment around tryptophan (Trp) and tyrosine (Tyr), which resulted in the conformational change of tyrosinase. In addition, fluorescence and molecular docking analysis indicated that PG bound to tyrosinase via hydrogen bonds (H‐bonds) and van der Waals force (vdW force). We herein recommended that PG might be a potential candidate drug for the treatment of melanin‐related diseases. [ABSTRACT FROM AUTHOR]

• DBD is used to explore a new way to optimize fuel atomization. • He-assisting DBD can reduce droplets size and increase spray angle. • Active-particle types in the atomization field are obtained. In order to study the influence law of active particles on atomization characteristics of aviation kerosene and explore the key technologies of plasma application in fuel atomization auxiliary, the dielectric barrier discharge plasma nozzle was independently designed, and the experiments of He plasma jet spectrum diagnosis and fuel atomization characteristic were carried out. The active particle composition of He plasma jet was explored, and the influence of He volume flow rate and peak voltage on electron excitation temperature, SMD and spray cone angle were studied. The results show that He plasma ionizes the air in the surrounding space to produce active particles such as OH, O and He Ⅰ atoms. The electron excitation temperature varies between 3100 and 7300 K and reaches the maximum when the peak voltage is 11 kV. The influence of electric field application and He volume flow changes on the atomization characteristics are very obvious, specifically, as the peak voltage increases, the SMD decreases and the spray cone angle increases. Under the high peak voltage (12–13 kV), the increasing trend of the spray cone angle gradually slows down and stabilizes. As the volume flow of He increases, the SMD decreases and the spray cone angle increases. The difference in oil supply pressure will affect the atomization effect of plasma excited fuel. The specific realization is that under △P inj = 0.05 MPa, the increase of He volume flow has little effect on the atomization effect. When △P inj = 0.15–0.35 MPa, the change of peak voltage has a greater impact on SMD, while at a lower △P inj (0.05–0.25 MPa), the change of peak voltage has a greater impact on the growth trend of the spray cone angle. [ABSTRACT FROM AUTHOR]

[Display omitted] • The interactions between engeletin with CYP3A4 and CYP2D6 have been investigated. • Results revealed that engeletin bound to CYP3A4 stronger than it did to CYP2D6. • The conformation and micro-environment of the two CYPs were changed after binding with engeletin. • Hydrogen bonding and van der Waals forces play major role in the binding process. The inhibitory effects of engeletin on the activities of human cytochrome P450 3A4 and 2D6 (CYP3A4 and CYP2D6) were investigated by enzyme kinetics, multi-spectroscopy and molecular docking. Engeletin was found to strongly inhibit CYP3A4 and CYP2D6, with the IC 50 of 1.32 μM and 2.87 μM, respectively. The inhibition modes of engeletin against CYP3A4 and CYP2D6 were a competitive type and a mixed type, respectively. The fluorescence of the two CYPs was quenched statically by engeletin, which was bound to CYP3A4 stronger than to CYP2D6 at the same temperature. Circular dichroism spectroscopy, three-dimensional fluorescence, ultraviolet–visible spectroscopy and synchronous fluorescence confirmed that the conformation and micro-environment of the two CYPs protein were changed after binding with engeletin. Molecular docking, ultraviolet–visible spectroscopy and the fluorescence data revealed that engeletin had strong binding affinity to the two CYPs through hydrogen and van der Waals forces. The findings here suggested that engeletin may cause the herb-drug interactions for its inhibition of CYP3A4 and CYP2D6 activities. [ABSTRACT FROM AUTHOR]

Abstract: The hot deformation behaviors of as-cast Ti–45Al–8.5Nb–(W,B,Y) alloy were studied. A mathematical model has been developed to predict the stress–strain curves of this high Nb containing TiAl based alloy during hot deformation. This model is based on a phenomenological representation of the shape of stress–strain curves, which can be represented by Zener–Hollomon parameter in a hyperbolic sinusoidal type equation. Material constants in the equation were expressed in polynomial form of strain; parameters in the polynomials were obtained by least-square method. The stress–strain curves obtained by this model are in good agreement with experimental results. [Copyright &y& Elsevier]

Abstract: The vast majority of patients with multiple sclerosis (MS) develop bladder control problems including urgency to urinate, urinary incontinence, frequency of urination, and retention of urine. Over 60% of MS patients show detrusor-sphincter dyssynergia, an abnormality characterized by obstruction of urinary outflow as a result of discoordinated contraction of the urethral sphincter muscle and the bladder detrusor muscle. In the current study we examined bladder function in female SWXJ mice with different defined levels of neurological impairment following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of central nervous system inflammation widely used in MS research. We found that EAE mice develop profound bladder dysfunction characterized by significantly increased micturition frequencies and significantly decreased urine output per micturition. Moreover, we found that the severity of bladder abnormalities in EAE mice was directly related to the severity of clinical EAE and neurologic disability. Our study is the first to show and characterize micturition abnormalities in EAE mice thereby providing a most useful model system for understanding and treating neurogenic bladder. [Copyright &y& Elsevier]

Key message: Based on the high-density variation map, we identified genome-level evidence for local adaptation and demonstrated that Siprr37 with transposon insertion contributes to the fitness of foxtail millet in the northeastern ecoregion. Adaptation is a robust way through which plants are able to overcome environmental constraints. The mechanisms of adaptation in heterogeneous natural environments are largely unknown. Deciphering the genomic basis of local adaptation will contribute to further improvement in domesticated plants. To this end, we describe a high-depth (19.4 ×) haplotype map of 3.02 million single nucleotide polymorphisms in foxtail millet (Setaria italica) from whole-genome resequencing of 312 accessions. In the genome-wide scan, we identified a set of improvement signals (including the homologous gene of OsIPA1, a key gene controlling ideal plant architecture) related to the geographical adaptation to four ecoregions in China. In particular, based on the genome-wide association analysis results, we identified the contribution of a pseudo-response regulator gene, SiPRR37, to heading date adaptation in foxtail millet. We observed the expression changes of SiPRR37 resulted from a key Tc1–Mariner transposon insertion in the first intron. Positive selection analyses revealed that SiPRR37 mainly contributed to the adaptation of northeastern ecoregions. Taken together, foxtail millet adapted to the northeastern region by regulating the function of SiPRR37, which sheds lights on genome-level evidence for adaptive geographical divergence. Besides, our data provide a nearly complete catalog of genomic variation aiding the identification of functionally important variants. [ABSTRACT FROM AUTHOR]

For electrically conductive adhesives (ECAs), it is critical to ensure high electrical conductivity and good adhesion reliability for practical applications in electronic products. In this study, high conductivity ECAs at low filler content were achieved by fully utilizing the synergistic effect of nano- and micro-scale fillers. Nanosilver-coated copper micronflakes (Ag@Cus) prepared by an electroless plating method were selected as the main conductive fillers. Silver nanowires (AgNWs) made by a simple one-step polyol method were dispersed as auxiliary conductive fillers in Ag@Cus, providing more possibilities for establishing a large number of conductive bridges. Furthermore, the curing process of matrix resin was predicted based on curing kinetics and was verified by corresponding experiments to determine the optimal curing parameters. The results show that the combination of AgNWs and Ag@Cus in ECAs can significantly reduce the bulk resistivity and percolation threshold compared with the single component. In particular, the bulk resistivity of ECAs filled with AgNWs and Ag@Cus (mass ratio 1:9) is as low as 9.42 × 10−5 Ω cm when the filler content is only 60 wt%. • T he combination of AgNWs and Ag@Cus in ECAs could significantly reduce the bulk resistivity and the percolation threshold compared with AgNWs or Ag@Cus individually. • AgNWs as one-dimensional nano-materials has the effect of lowering the percolation threshold, while Ag@Cus as micronflakes has the effect of reducing the bulk resistivity. • Thus, the bulk resistivity of ECAs could reach a low value of 9.42 × 10−5 Ω cm when the filler content was only 60 wt% in bi-compound ECAs filled with AgNWs and Ag@Cus (the mass ratio is 1:9). [ABSTRACT FROM AUTHOR]

Okanin is a major flavonoid found in Coreopsis tinctoria Nutt., arousing huge interest recently for its considerable biological characteristics including antioxidant, antineurotoxic, and antidiabetic activities. An ultrahigh performance liquid chromatography triple-quadrupole tandem mass spectrometry (UPLC-MS) was successfully used to determine okanin in rat plasma after oral administration of okanin. Bavachalcone acted as an internal standard (IS). By gradient elution, IS and analyte were separated on a C18 column for 7 min at a flow rate of 0.25 mL/min with acetonitrile-0.1% acetic acid mobile phase. The stability, matrix effect, extraction recovery, accuracy, precision, linearity, and selectivity of the method were firstly demonstrated. The major pharmacokinetic parameters of okanin in rat plasma were then measured using the developed UPLC-MS method. An UPLC-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was finally established to obtain the specific and accurate mass of okanin in rat plasma after oral administration, and its proposed fragmentation was further elaborated. [ABSTRACT FROM AUTHOR]

Damage at an electromagnetic railgun’s initial position during launch affects the life of the rail and launcher as well as the launch speed and efficiency. Therefore, this study investigated such damage through electromagnetic railgun experiments. Analyses of metallographic specimens and surface composition as well as 3-D scanning and reconstruction of damaged parts indicate that the damage is a thermal effect mainly caused by transition ablation. Transition ablation problems caused by insufficient initial contact pressure, large rail spacing, and insufficient rail strength are analyzed and corresponding improvement measures are suggested. Finally, the effectiveness of these measures is verified through experiments to guide the design, manufacture, and application of electromagnetic railguns. [ABSTRACT FROM AUTHOR]

Recent studies suggested smooth muscle contraction may involve mechanisms besides the myosin regulatory light chain (MLC) phosphorylation-induced actomyosin crossbridge cycling. This study aims to determine if focal adhesion kinase (FAK) activation is involved in mouse detrusor muscle contraction. The mouse detrusor muscle strips were preincubated with PF-573228 (2 μM), latrunculin B (1 μM), or the same volume of vehicle (DMSO) for 30 min. The contractile responses to KCl (90 mM), electrical field stimulation (EFS, 2–32 Hz), or carbachol (CCh, 10−7.5-10−4.5 M) were measured. In a separate experiment, the phosphorylated FAK (p-FAK) and MLC (p-MLC) levels were measured in the detrusor strips stimulated with CCh (10 μM) after incubation with PF-573228 or vehicle (DMSO) compared to those with vehicle incubation but without CCh stimulation. KCl-induced contractile responses decreased significantly after incubation with PF-573228 or latrunculin B compared to the corresponding vehicle-treated strips (p < 0.0001). The contractile responses induced by EFS were markedly inhibited by preincubation with PF-573228 at 8, 16, and 32 Hz (p < 0.05) or latrunculin B at 16 and 32 Hz (p < 0.01). Following the application of PF-573228 or Latrunculin B, CCh-induced dose-response contractions were lower than the corresponding vehicle group (p = 0.0021 and 0.0003, respectively). Western blot examination showed that CCh stimulation enhanced the expression of p-FAK and p-MLC, while preincubation with PF-573228 prevented the increase of p-FAK but not p-MLC. In conclusion, FAK activation involves tension development induced by contractile stimulation in the mouse detrusor muscle. This effect is likely caused by promoting actin polymerization rather than elevating MLC phosphorylation. [ABSTRACT FROM AUTHOR]

Early studies showed that the irregular operations of the center pivot sprinkling system would decrease its uniformity while the reason was lack of discussion. Taking Herman-Hein uniformity coefficient (CUH) and Distribution uniformity coefficient (DU) as evaluation indicators, the reason that irregular operation management and configurations can decrease the uniformity of center pivot sprinkling irrigation was discussed and the impact on maize yield was tested. The reasons for such decrease in uniformity include: (1) With the increase of moving speed, the effect of sprinkling overlaying became worse, which resulted in the lower uniformity of sprinkling irrigation; (2) With the increase of head pressure, the inlet pressure could be adjusted to the same pressure by pressure regulator, which kept the uniformity of sprinkling irrigation constant; (3) When end gun worked abnormally, total head pressure decreased, which led to the decrease of sprinkling irrigation's uniformity; (4) When pressure regulator worked abnormally, the water flow was subject to great pressure loss, which could decrease the uniformity of sprinkling irrigation; (5) When pressure regulator was uninstalled, significant abnormality of sprinkling irrigation depth occurred, resulting in the decreasing of sprinkling irrigation's uniformity; (6) Different types of nozzles could produce different uniformity of sprinkling irrigation, which was due to different structures of micro-nozzles; (7) Due to lower uniformity, at the seedling stage of maize, both height and seedling emergence rate decreased. Final yield decreased by 18.35%. This study is important to the proper use and the improvement of configuration selection and field management of center pivot sprinkling system. [ABSTRACT FROM AUTHOR]