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Rotary blood pumps (RBPs) operating at a constant speed generate non-physiologic blood pressure and flow rate, which can cause endothelial dysfunction, leading to adverse clinical events in peripheral blood vessels and other organs. Notably, pulsatile working modes of the RBP can increase vascular pulsatility to improve arterial endothelial function. However, the laws and related mechanisms of differentially regulating arterial endothelial function under different pulsatile working modes are still unclear. This knowledge gap hinders the optimal selection of the RBP working modes. To address these issues, this study developed a multi-element in vitro endothelial cell culture system (ECCS), which could realize in vitro cell culture effectively and accurately reproduce blood pressure, shear stress, and circumferential strain in the arterial endothelial microenvironment. Performance of this proposed ECCS was validated with numerical simulation and flow experiments. Subsequently, this study investigated the effects of four different pulsation frequency modes that change once every 1-4-fold cardiac cycles (80, 40, 80/3, and 20 cycles per min, respectively) of the RBP on the expression of nitric oxide (NO) and reactive oxygen species (ROS) in endothelial cells. Results indicated that the 2-fold and 3-fold cardiac cycles significantly increased the production of NO and prevented the excessive generation of ROS, potentially minimizing the occurrence of endothelial dysfunction and related adverse events during the RBP support, and were consistent with animal study findings. In general, this study may provide a scientific basis for the optimal selection of the RBP working modes and potential treatment options for heart failure. [ABSTRACT FROM AUTHOR]

Fifty-one learning strategies were developed and validated in this study to make language learners more knowledgeable about unfamiliar environments. The study tested the effectiveness of the strategies in improving the creativity of students. 75 university students participated in the study and they were divided into three groups: (1) students who learned in unfamiliar learning environments without familiarization strategies; (2) students who learned in unfamiliar learning environments and used familiarization strategies; and (3) students who learned in familiar learning environments. All students learned vocabulary, grammar, sentence patterns and how to write descriptive essays in class. After class, they applied newly learned knowledge by describing people, objects and situations in the real world using mobile devices. The content of students' essays was compared across three groups and the results showed that students in Group 2 and Group 3 had better creativity scores than students in Group 1. The results indicated that students' creativity is affected by their familiarity with the environment. Therefore, it is suggested that student familiarization with learning sites needs to be considered when designing learning activities in the real world. Educators should provide familiarization strategies to students when learning in unfamiliar learning environments. [ABSTRACT FROM AUTHOR]

Black rockfish (Sebastes schlegelii) is one of the most important marine economic viviparous fishes. Recently, germplasm degradation and genetic diversity reduction have occurred due to overfishing and long-term artificial breeding. Germ cell transplantation combined with cryopreservation may be an alternative way to protect genetic resources. However, in viviparous fish that undertake fertilization and embryo development in vivo, transplantation is more difficult than in oviparous fish, including selection of transplantation stage, isolation of germ stem cells, and preparation of sterile recipients. This seriously restricts the development of viviparous transplantation. Therefore, in this study, we aimed to explore a transplantation method suitable for these species. Donor cells were isolated from cryopreserved whole testes of 300-400 g male Sebastes schlegelii in May, labeled by PKH26, and intra-peritoneally transplanted into allogeneic larvae at 5-10 days post-birth. Subsequently, the development of donor-derived cells in recipients were continuously detected by fluorescence labeling, histology, microsatellite markers, and fecundity tests. The results showed that donors were rich in spermatogonia (75%) and recipients maintained a high survival rate after transplantation, with a rate of >20% at sexual maturity. Further, donor-derived cells successfully migrated (100%), colonized, and incorporated into the developing recipient gonad (93.33%). Finally, transplanted recipients could normally develop and differentiate into male and female individuals, with donor-derived gametes found in 65.38% of mature recipients. In the present study, we first establish a simple and suitable transplantation method for Sebastes schlegelii using immature males and specific larvae, which will serve as a promising tool in the protection of germplasm resources for this transplantationrestricted marine viviparous species. [ABSTRACT FROM AUTHOR]

Theaflavins (TFs), as the major polyphenolic components of fermented tea, possess beneficial effects on human health. In this study, the effervescent tablets based on theaflavins were developed. The optimal formulation of TF effervescent tablets was obtained by response surface methodology with the Box-Behnken design. Then, the physiochemical properties were evaluated, including hardness, friability, effervescent time and pH of the solution. At last, the antioxidant ability of TF effervescent tablets was studied through DPPH and ABTS radical scavenging assay. According to the results, the optimal formulation of the tablets contained TF powder 9.09%, disintegrating agent 43.80% (the weight ratio of citric acid and sodium bicarbonate was 1:1), aspartame 1.86%, PEG-600 3%, and mannitol in balance. With the wet granulation method, the TF effervescent tablets displayed suitable hardness, fast disintegration time, good color, pleasant taste and high antioxidant activity. This study demonstrated that the TF effervescent tablets could be a valuable product for the supplement market and contribute to promoting practical application of TFs. [ABSTRACT FROM AUTHOR]

It has been recognized that depth of invasion (DOI) is closely associated with patient survival for most types of cancer. The purpose of this study was to determine the DOI optimal cutoff value and its prognostic value in laryngeal squamous carcinoma (LSCC). Most importantly, we evaluated the prognostic performance of five candidate modified T-classification models in patients with LSCC. LSCC patients from Harbin Medical University Cancer Hospital and Chinese Academy of Medical Sciences Cancer Hospital were divided into training group (n = 412) and validation group (n = 147). The primary outcomes were overall survival (OS) and relapse-free survival (RFS), and the effect of DOI on prognosis was analyzed using a multivariable regression model. We identified the optimal model based on its simplicity, goodness of fit and Harrell's consistency index. Further independent testing was performed on the external validation queue. The nomograms was constructed to predict an individual's OS rate at one, three, and five years. In multivariate analysis, we found significant associations between DOI and OS (Depth of Medium-risk invasion HR, 2.631; P < .001. Depth of high-risk invasion: HR, 5.287; P < .001) and RFS (Depth of high-risk invasion: HR, 1.937; P = .016). Model 4 outperformed the American Joint Committee on Cancer (AJCC) staging system based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves. Inclusion of DOI in the current AJCC staging system can improve the differentiation of T classification in LSCC patients. [ABSTRACT FROM AUTHOR]

The dynamic rheological properties of peanut protein isolate (PPI) suspension and acid-induced PPI gels were studied. In frequency sweep test, the storage modulus (G') and the loss modulus (G") of PPI aggregation suspensions at different concentrations increased with the increase of frequency. The steady state shear flow test showed that PPI aggregation suspension had a thinning behavior of the shear, and the image of steady shear curve fitted the Carreau model. After gel formation, acid-induced PPI gels showed a typical Type I behavior (strain thinning) in strain sweep test, meaning that PPI gel got easily broken down, and there was a very small opportunity for the protein molecules to re-establish the network. Compared with the strain sweep of PPI aggregation suspensions and gels, the range of the storage modulus existed a dramatic difference, which could get about tenfold. As the frequency increased, both elasticity and viscosity increased in frequency sweep test, which indicated that the frequency dependence of the storage modulus increased with the increase of concentration. [ABSTRACT FROM AUTHOR]

The karyotype is highly important for diagnosis and prognosis in myelodysplastic syndrome (MDS). The objective of the present study was to investigate the cytogenetic characteristics of patients with MDS in China. The karyotypes of 665 Chinese patients with MDS were analyzed, and it was identified that 298 cases (298/665, 44.8%) had abnormal karyotypes. Among the 298 patients with abnormal karyotypes, the 75 patients with trisomy 8 (+8) constituted the most common subset (75/298, 25.2%). The incidence of abnormal karyotypes was significantly higher in patients who were ≥51 years old compared with those <51 years old, (54.8 vs. 34.7%, respectively; P<0.05). Based on World Health Organization (WHO) classification-based Prognostic Scoring System (WPSS) criteria, the incidence of poor-prognosis karyotypes was significantly higher (17.4 vs. 5.4%; P<0.05) in the older patient group, and based on the Revised International Prognostic Scoring System (IPSS-R) criteria, the incidence of poor-/very poor-prognosis karyotypes was also significantly higher (17.4 vs. 6.6%; P<0.05) in patients ≥51 years old compared with younger ones. Based on the WHO classification of MDS subtypes, the incidence of abnormal karyotypes in patients with high percentages of bone marrow (BM) blasts [excess blasts (EB)-I + EB-II, ≥5% blasts] was significantly higher than that in patients with low percentages of BM blasts (those with single lineage dysplasia + multilineage dysplasia, <5% blasts) (62.5 vs. 36.0%; P<0.05). The incidence of poor-prognosis karyotypes based on WPSS criteria was significantly higher in patients with high percentages of BM blasts than those with low percentages (22.0 vs. 6.9%, respectively; P<0.05), and the incidence of poor-/very poor-prognosis karyotypes based on IPSS-R criteria was also significantly higher (23.0 vs. 7.4%, respectively; P<0.05). These results demonstrate that +8 is the most common abnormal karyotype in Chinese patients with MDS. Age and the percentage of BM blasts are associated with the incidence of both abnormal karyotypes and karyotypes with poor prognosis. The results of cytogenetic abnormalities in this study will supplement the data on patients of MDS in China. [ABSTRACT FROM AUTHOR]

In this paper, the necessary and sufficient conditions for the existence of traveling wave solutions are derived for a class of diffusive disease-transmission models with network structures. The existence of traveling semifronts is obtained by Schauder's fixed-point theorem, and these traveling semifronts are shown to be bounded by transforming the boundedness problem into the classification problem of nonnegative solutions to a linear elliptic system on R. To overcome the reducibility problem arising in the proofs, Harnack's inequality for positive supersolutions on R is proved. [ABSTRACT FROM AUTHOR]

NAD and its reduced form NADH function as essential redox cofactors and have major roles in determining cellular metabolic features. NAD can be synthesized through the deamidated and amidated pathways, for which the key reaction involves adenylylation of nicotinic acid mononucleotide (NaMN) and nicotinamide mononucleotide (NMN), respectively. In Escherichia coli, NAD de novo biosynthesis depends on the protein NadD-catalyzed adenylylation of NaMN to nicotinic acid adenine dinucleotide (NaAD), followed by NAD synthase-catalyzed amidation. In this study, we engineered NadD to favor NMN for improved amidated pathway activity. We designed NadD mutant libraries, screened by a malic enzyme-coupled colorimetric assay, and identified two variants, 11B4 (Y84V/Y118D) and 16D8 (A86W/Y118N), with a high preference for NMN. Whereas in the presence of NMN both variants were capable of enabling the viability of cells of E. coli BW25113-derived NADauxotrophic strain YJE003, for which the last step of the deamidated pathway is blocked, the 16D8 expression strain could grow without exogenous NMN and accumulated a higher cellular NAD(H) level than BW25113 in the stationary phase. These mutants established fully active amidated NAD biosynthesis and offered a new opportunity to manipulate NAD metabolism for biocatalysis and metabolic engineering. IMPORTANCE Adenylylation of nicotinic acid mononucleotide (NaMN) and adenylylation of nicotinamide mononucleotide (NMN), respectively, are the key steps in the deamidated and amidated pathways for NAD biosynthesis. In most organisms, canonical NAD biosynthesis follows the deamidated pathway. Here we engineered Escherichia coli NaMN adenylyltransferase to favor NMN and expressed the mutant enzyme in an NAD-auxotrophic E. coli strain that has the last step of the deamidated pathway blocked. The engineered strain survived in M9 medium, which indicated the implementation of a functional amidated pathway for NAD biosynthesis. These results enrich our understanding of NAD biosynthesis and are valuable for manipulation of NAD homeostasis for metabolic engineering. [ABSTRACT FROM AUTHOR]

In this work, we propose novel epidemic models (named, susceptible-infected-recovered-susceptiblebacteria) for cholera dynamics by incorporating a general formulation of bacteria growth and spatial variation. In the first part, a generalized ordinary differential equation (ODE) model is presented and it is found that bacterial growth contributes to the increase in the basic reproduction number, R0. With the derived basic reproduction number, we analyse the local and global dynamics of the model. Particularly, we give a rigorous proof on the endemic global stability by employing the geometric approach. In the second part, we extend the ODE model to a partial differential equation (PDE) model with the inclusion of diffusion to capture the movement of human hosts and bacteria in a heterogeneous environment. The disease threshold of this PDE model is studied again by using the basic reproduction number. The results on the threshold dynamics of the ODE and PDE models are compared, and verified through numerical simulation. Additionally, our analysis shows that incorporating diffusive spatial spread does not produce a Turing instability when R0 associated with the ODE model is less than the unity. [ABSTRACT FROM AUTHOR]

Liquid/liquid second-dispersion signifies the process of breaking dispersed droplets, for the purpose of further reducing the droplet size. This study introduces a systemic experimental study on the second-dispersion process in different constricted microchannels and presents the flowing behaviors of liquid plugs passing through them. Both breakup, non-breakup and their transition of plugs were observed at the operating conditions of Ca ranging from 0.0002 to 0.025 and Re ranging from 0.74 to 27.3 in the orifice. Main factors influencing the plug breakup process, such as surfactant concentration, plug length, flow rate, viscosity and channel geometry, were carefully examined. We found the liquid/liquid second-dispersion process, driven by the capillary pressure criterion, is both a statically confined and dynamical confined process. To realize second-dispersion, the hydraulic radius ratio of downstream microchannel to constrictive orifice should be larger than 1.89 and the operating condition should be lower than the critical capillary numbers (~10-3) of continuous phase and dispersed phase. We find these critical capillary numbers reduce as the rising of hydraulic radius of the orifice but changed little with the enlargement of downstream microchannel. The orifice geometry also dominates the daughter droplets, whose radii are at least two times of the orifice hydraulic radius. [ABSTRACT FROM AUTHOR]

How brain functions degenerate in the face of progressive cell loss is an important issue that pertains to neurodegenerative diseases and basic properties of neural networks. We developed an automated system that uses two-photon microscopy to detect rhythmic neurons from calcium activity, and then individually laser ablates the targets while monitoring network function in real time. We applied this system to the mammalian respiratory oscillator located in the pre-Bötzinger Complex (preBötC) of the ventral medulla, which spontaneously generates breathing-related motor activity in vitro. Here, we show that cumulatively deleting preBötC neurons progressively decreases respiratory frequency and the amplitude of motor output. On average, the deletion of 120 ± 45 neurons stopped spontaneous respiratory rhythm, and our data suggest ≈82% of the rhythm-generating neurons remain unlesioned. Cumulative ablations in other medullary respiratory regions did not affect frequency but diminished the amplitude of motor output to a lesser degree. These results suggest that the preBötC can sustain insults that destroy no more than ≈18% of its constituent interneurons, which may have implications for the onset of respiratory pathologies in disease states. [ABSTRACT FROM AUTHOR]

A novel-designed compact, ultrafast electro-optic slow light modulator based on two-dimensional coupled photonic crystal resonator arrays (2D CPCRAs) has been studied. The 2D CPCRAs, realized in silicon-on-insulator (SOI) slabs with nonlinear polymer as filling material, exhibit a single guided mode with low group velocity in all crystal directions. We realize fast electro-optic tuning of the slow mode in a wide frequency range with low modulating voltage in this structure. Numerical analysis shows that the frequency shift is nearly linearly increasing with the applied voltage. In addition, for a certain frequency, changing the modulating voltage can tune the group delay of slow mode easily. [ABSTRACT FROM AUTHOR]

A series of three novel 2,3,9,10,16,17,24,25-octakis(octyloxycarbonyl)phthalocyanine compounds M[Pc(COOC8H17)8] (M = 2H, Cu, Zn) (1-3) have been synthesized via the cyclic tetramerization of 4,5-di(octyloxycarbonyl)phthalonitrile, which was obtained by a newly developed procedure with ο-xylene as starting material, promoted with organic base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the absence and presence of metal salt like M(acac)2·H2O (M = Cu, Zn) in n-octanol at 120 °C. In addition to elemental analysis, these novel octakis(octyloxycarbonyl)-substituted phthalocyanine compounds have been characterized by a series of spectroscopic methods. The electrochemistry of these compounds was also studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods. A significant shift to the positive direction for both the first oxidation and the first reduction of compound 1, relative to H2Pc, reveals the electron-withdrawing nature of octyloxycarbonyl groups attached to the peripheral positions of phthalocyanine. The effect of peripheral octyloxycarbonyl substitution on the electrochemistry of the series of phthalocyanines 1-3 has been reasonably explained by theoretical calculation results using the density functional theory (DFT) method. [ABSTRACT FROM AUTHOR]

Intense 1.8?µm and efficient 1.47?µm infrared emissions have been recorded in Tm3+-doped alkali-barium-bismuth-tellurite (LKBBT) glasses with lower phonon energies under the excitation of a 792?nm diode laser. The maximum emission cross-sections for the 1.8 and 1.47?µm emission bands are derived to be 6.643 × 10?21and 3.551 × 10?21?cm2and the peak values are obviously higher than those in Tm3+-doped ZBLAN fluoride and TBSN tellurite glasses, respectively. In low concentration doping, the full-widths at half-maximum (FWHMs) of the two emission bands are 206?nm and 109?nm, respectively, and peak intensity ratio between them is about 2. When the doping concentration increases to 1?wt%, the peak intensity ratio exceeds 7 and the quantum efficiency of 3H4level is only 64.6% due to the cross-relaxation process [3H4, 3H6] ? [3F4, 3F4], which benefits to achieve powerful 1.8?µm emission. The efficient and broad 1.8 and 1.47?µm infrared emission bands indicate that Tm3+-doped LKBBT glasses are suitable materials in developing S- and U-band amplifiers and 1.8?µm infrared laser. [ABSTRACT FROM AUTHOR]

c-Abl and atm have been implicated in cell responses to DNA damage and oxidative stress. However, the molecular mechanisms by which they regulate oxidative stress response remain unclear. In this report, we show that deficiency of c-Abl and deficiency of ATM differentially altered cell responses to oxidative stress by induction of antioxidant protein peroxiredoxin I (Prx I) via Nrf2 and cell death, both of which required protein kinase C (PKC) δ activation and were mediated by reactive oxygen species, c-abl-/- osteoblasts displayed enhanced Prx I induction, elevated Nrf2 levels, and hypersusceptibility to arsenate, which were reinstated by reconstitution of c-Abl; Atm-/- osteoblasts showed the opposite. These phenotypes correlated with increased PKC δ expression in c-abl-/- osteoblasts and decreased PKC δ expression in Atm-/- cells, respectively. The enhanced responses of c-abl-/- osteoblasts could be mimicked by overexpression of PKC δ in normal cells and impeded by inhibition of PKC δ, and diminished responses of Atm-/- cells could be rescued by PKC δ overexpression, indicating that PKC δ mediated the effects of c-Abl and ATM in oxidative stress response. Hence, our results unveiled a previously unrecognized mechanism by which c-Abl and Atm participate in oxidative stress response. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between hepatic venous pressure gradient (HVPG) baseline and the response rate of cirrhotic in patients who received carvedilol treatment. Methods: In total 48 cirrhotic patients with a basic HVPG value greater than 12 mmHg were included (from July 2011 to October 2014). All patients received carvedilol treatment and underwent the second HVPG measurement 7 days later. In the following, all participants received an endoscopic variceal ligation (EVL) treatment. Results: HVPG was significantly reduced from 16.04 ± 3.10 to 12.76 ± 5.26 mmHg following carvedilol treatment. The response rate was about 58.33% (28/48). The response rate of the HVPG < 16 mmHg group (71.4%) was significantly higher than that of the HVPG ≥ 16 mmHg group (40%) (P < 0.05). Patients were followed up for a median of 26 months, ranged from 6 to 33 months. During the follow-up period (two years), the rebleeding rate was 9.97% and 49.56% in HVPG < 16 and HVPG ≥ 16 mmHg groups, respectively, with a statistically significant difference (P = 0.004). Also, the mortality rate (at 2 years) was 5.26% and 21.05%, respectively, which was significant (P = 0.035). Conclusions: This study demonstrated that the response rate of carvedilol on portal hypertension may be affected by the HVPG baseline, and the carvedilol was effective in reducing HVPG, especially for those with a HVPG < 16 mmHg. [ABSTRACT FROM AUTHOR]

Dysregulation of angiogenesis can be caused by hypoxia, which may result in severe diseases of the heart, including coronary artery disease. Hypoxia-inducible factor 1 (HIF-1) modulates angiogenesis via the regulation of several angiogenic factors. However, the underlying mechanism of hypoxia-induced angiogenesis remains unknown. In the present study, it was hypothesized that long non-coding RNA?(lncRNA) non-coding RNA activated by DNA damage (NORAD) may serve a role in the process of angiogenesis via the regulation of microRNA (miR)-590-3p under hypoxic conditions. The effect of NORAD and miR- 590-3p on cell viability and properties associated with angiogenesis, including cell migration and tube formation in human umbilical vein endothelial cells (HUVEC s) under hypoxic conditions, were assessed. Potential downstream angiogenic factors of miR- 590-3p were also determined by molecular experiments. It was identified that NORAD expression was upregulated and miR- 590-3p expression was downregulated in hypoxia-exposed HUVEC s, and also in myocardial infarction (MI) left ventricle tissues in mice. Moreover, downregulation of NORAD expression resulted in decreased cell viability and angiogenic capacity, but further knocking down miR- 590-3p expression reversed these alterations, resulting in increased cell migration and tube formation in HUVEC s under hypoxic conditions for 24 h. It was demonstrated that NORAD overexpression also increased cell vitality and tube-formation capacity. Furthermore, NORAD was identified to bind with miR- 590-3p directly, and miR- 590-3p was shown to target certain proangiogenic agents, such as vascular endothelial growth factor (VEGF)A, fibroblast growth factor (FGF)1 and FGF2 directly. Therefore, the present results suggested that lncRNA NORAD may bind with miR- 590-3p to regulate the angiogenic ability of HUVEC s via the regulation of several downstream proangiogenic factors under hypoxia. Thus, the lncRNA NORAD/miR- 590-3p axis may be a novel regulatory pathway in the angiogenic mechanisms in HUVEC s, which highlights a potentially novel perspective for treating ischemia/hypoxia-induced angiogenic diseases. [ABSTRACT FROM AUTHOR]

The mitochondrial enzyme glutaminase (GLS) is frequently upregulated during tumorigenesis and is being evaluated as a target for cancer therapy. GLS catalyzes the hydrolysis of glutamine to glutamate, which then supplies diverse metabolic pathways with carbon and/or nitrogen. Here, we report that SIRT5, a mitochondrial NAD+-dependent lysine deacylase, plays a key role in stabilizing GLS. In transformed cells, SIRT5 regulates glutamine metabolism by desuccinylating GLS and thereby protecting it from ubiquitin-mediated degradation. Moreover, we show that SIRT5 is up-regulated during cellular transformation and supports proliferation and tumorigenesis. Elevated SIRT5 expression in human breast tumors correlates with poor patient prognosis. These findings reveal a mechanism for increasing GLS expression in cancer cells and establish a role for SIRT5 in metabolic reprogramming and mammary tumorigenesis. [ABSTRACT FROM AUTHOR]

Microchannel emulsification requires large amounts of surfactant to prevent coalescence and improve emulsions lifetime. However, most numerical studies have considered surfactant-free mixtures as models for droplet formation in microchannels, without taking into account the distribution of surfactant on the droplet surface. In this paper, we investigate the effects of nonuniform surfactant coverage on the microfluidic flow pattern using an extended lattice-Boltzmann model. This numerical study, supported by micro-particle image velocimetry experiments, reveals the likelihood of uneven distribution of surfactant during the droplet formation and the appearance of a stagnant cap. The Marangoni effect affects the droplet breakup by increasing the shear rate. According to our results, surfactant-free and surfactant-rich droplet formation processes are qualitatively different, such that both the capillary number and the Damköhler number should be considered when modeling the droplet generation in microfluidic devices. The limitations of traditional volume and pressure estimation methods for determining the dynamic interfacial tension are also discussed on the basis of the simulation results. [ABSTRACT FROM AUTHOR]

Background: Pearl oyster Pinctada fucata martensii is cultured for producing round nucleated pearls. Pearl production involves a surgical operation where a mantle tissue graft from a donor oyster and a round nucleus are implanted in the gonad of a host oyster. Whether the mantle graft implanted in the gonad of a host oyster contributes to the formation of a pearl sac that secretes pearl nacre to form a pearl should be determined. In April 2012, two full-sib families were separately used as donor and host oysters for a nucleus insertion operation. The pearl sac was sampled from the host oysters at day 60 after nucleus operation. A large number of simple sequence repeat (SSR) markers were developed using Illumina HiSeq™ 2000 platform. The two full-sib families were also used to mine diagnostic SSR markers for genotyping donor oyster, host oyster, and pearl sac. Results: A total of 3168 microsatellite lociwere identified in 39,078 unigenes, and 1977 SSR primerswere designed by Primer 3.0. Forty-seven SSR primers were validated, and the rate of successful amplification was 72.3%. Two diagnostic SSR primers could successfully genotype pearl sac, donor oyster, and host oyster. Donor and host oysters were both homogenous, and the alleles in pearl sac were identical to those in donor and host oysters. Conclusions: The present results confirmed that themantle graft implanted in the gonad of host oyster contributed to the formation of the pearl sac in pearl oyster P. fucata martensii. [ABSTRACT FROM AUTHOR]

Using a hydrothermal synthesis, the self-assembly of Mn[sup II] ions and 1,4-bis(1-imidazol-yl)-2,5-dimethyl benzene with two dicarboxylate ligands, 2-nitrobenzene-1,4-dicarboxylic acid (2-H[sub 2]ata) and 5-methylbenzene-1,3-dicarboxylic acid (5-CH[sub 3]-H[sub 2]ip) constructed two interesting coordination polymers: [Mn(2-ata)(bimb)][sub n] (1) and {[Mn(5-CH[sub 3]-ip) (bimb)[sub 1 5]]•2H[sub 2]O}[sub n] (2), where bimb refers to 1,4-bis(1-imidazol-yl)-2,5-dimethyl benzene. Their structures were determined by single-crystal X-ray diffraction, elemental analysis, and infrared spectroscopy. Complex 1 exhibits a 2-fold interpenetrated pcu net. Complex 2 shows an unusual polycatenated 2D+2D → 3D framework. In addition, the solid-state photoluminescent properties of 1 and 2 were investigated at room temperature. [ABSTRACT FROM AUTHOR]

The IGF family is essential for normal embryonic and postnatal development and plays important roles in the immune system, myogenesis, bone metabolism and other physiological functions, which makes the study of its structure and biological characteristics important. Tianzhu white yak (Bos grunniens) domesticated under alpine hypoxia environments, is well adapted to survive and grow against severe hypoxia and cold temperatures for extended periods. In this study, a full coding sequence of the IGF2 gene of Tianzhu white yak was amplified by reverse transcription PCR and rapid-amplification of cDNA ends (RACE) for the first time. The cDNA sequence revealed an open reading frame of 450 nucleotides, encoding a protein with 179 amino acids. Its expression in different tissues was also studied by Real time PCR. Phylogenetic tree analysis indicated that yak IGF2 was similar to Bos taurus, and 3D structure showed high similarity with the human IGF2. The putative full CDS of yak IGF2 was amplified by PCR in five tissues, and cDNA sequence analysis showed high homology to bovine IGF2. Moreover the super secondary structure prediction showed a similar 3D structure with human IGF2. Its conservation in sequence and structure has facilitated research on IGF2 and its physiological function in yak. [ABSTRACT FROM AUTHOR]

We consider the spread of an infectious disease in a heterogeneous environment modeled as a network of patches. We focus on the invasibility of the disease, as quantified by the corresponding value of an approximation to the network basic reproduction number, R0, and study how changes in the network structure affect the value of R0. We provide a detailed analysis for two model networks, a star and a path, and discuss the changes to the corresponding network structure that yield the largest decrease in R0. We develop both combinatorial and matrix analytic techniques, and we illustrate our theoretical results by simulations with the exact R0. [ABSTRACT FROM AUTHOR]

Faithful chromosome segregation during mitosis is critical for maintaining genome integrity in cell progeny and relies on accurate and robust kinetochore-microtubule attachments. The NDC80 complex, a tetramer comprising kinetochore protein HEC1 (HEC1), NDC80 kinetochore complex component NUF2 (NUF2), NDC80 kinetochore complex component SPC24 (SPC24), and SPC25, plays a critical role in kinetochore-microtubule attachment. Mounting evidence indicates that phosphorylation of HEC1 is important for regulating the binding of the NDC80 complex to microtubules. However, it remains unclear whether other post-translational modifications, such as acetylation, regulate NDC80-microtubule attachment during mitosis. Here, using pulldown assays with HeLa cell lysates and site-directed mutagenesis, we show that HEC1 is a bona fide substrate of the lysine acetyltransferase Tat-interacting protein, 60 kDa (TIP60) and that TIP60-mediated acetylation of HEC1is essential for accurate chromosome segregation in mitosis. We demonstrate that TIP60 regulates the dynamic interactions between NDC80 and spindle microtubules during mitosis and observed that TIP60 acetylates HEC1 at two evolutionarily conserved residues, Lys-53 and Lys-59. Importantly, this acetylation weakened the phosphorylation of the N-terminal HEC1(1-80) region at Ser-55 and Ser-62, which is governed by Aurora B and regulates NDC80-microtubule dynamics, indicating functional cross-talk between these two post-translation modifications of HEC1. Moreover, the TIP60-mediated acetylation was specifically reversed by sirtuin 1 (SIRT1). Taken together, our results define a conserved signaling hierarchy, involving HEC1, TIP60, Aurora B, and SIRT1, that integrates dynamic HEC1 acetylation and phosphorylation for accurate kinetochore-microtubule attachment in the maintenance of genomic stability during mitosis. [ABSTRACT FROM AUTHOR]

Digestion in the stomach depends on acidification of the lumen. Histamine-elicited acid secretion is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. Our recent study revealed the functional role of PKA-MST4-ezrin signaling axis in histamine-elicited acid secretion. However, it remains uncharacterized how the PKA-MST4-ezrin signaling axis operates the insertion of H,KATPases into the apical plasma membranes of gastric parietal cells. Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr545. Histamine stimulation activates MST4 and promotes MST4 interaction with ACAP4. ACAP4 physically interacts withMST4and is a cognate substrate of MST4 during parietal cell activation. The phosphorylation site of ACAP4 by MST4 was mapped to Thr545 by mass spectrometric analyses. Importantly, phosphorylation of Thr545 is essential for acid secretion in parietal cells because either suppression of ACAP4 or overexpression of non-phosphorylatable ACAP4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, persistent overexpression of MST4 phosphorylationdeficient ACAP4 results in inhibition of gastric acid secretion and blockage of tubulovesicle fusion to the apical membranes. Significantly, phosphorylation of Thr545 enables ACAP4 to interact with ezrin. Given the location of Thr545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction. Taken together, these results define a novel molecular mechanism linking the PKA-MST4-ACAP4 signaling cascade to polarized acid secretion in gastric parietal cells. [ABSTRACT FROM AUTHOR]

We collected flying fish (Exocoetus volitans) from the South China Sea to determine whether fish scale isotope values correlate with those from muscle, and discuss relevant eco-environmental implications. A significant positive correlation was determined between fish scales and muscle δ13C and δ15N, rendering a fish scale an alternative to muscle tissue for stable isotope analysis. However, muscle and scale isotopic offsets should be fully considered when using δ13C and δ15N to analyze the actual trophic level of fish and their food source. The average offsets of δ13C and δ15N between muscles and scales are -2.1 ± 0.5‰ and 2.3 ± 0.6‰, respectively, though these values vary slightly with fish mass. Weak correlations were found between δ13C and δ15N, both in the flying fish muscle and scales, suggesting that other factors are influencing δ13C and δ15N. Fish δ15N also correlates with the size of individuals, while δ13C reflects the marine habitat. Based on our data, it appears that more eco-environmental processes can be revealed from modern or ancient flying fish scales. [ABSTRACT FROM AUTHOR]

Breathing in mammals depends on rhythms that originate from the preBötzinger complex (preBötC) of the ventral medulla and a network of brainstem and spinal premotor neurons. The rhythm-generating core of the preBötC, as well as some premotor circuits, consist of interneurons derived from Dbxl-expressing precursors (Dbxl neurons), but the structure and function of these networks remain incompletely understood. We previously developed a cell-specific detection and laser ablation system to interrogate respiratory network structure and function in a slice model of breathing that retains the preBötC, the respiratory-related hypoglossal (XII) motor nucleus and XII premotor circuits. In spontaneously rhythmic slices, cumulative ablation of Dbxl preBötC neurons decreased XII motor output by -50% after -15 cell deletions, and then decelerated and terminated rhythmic function altogether as the tally increased to -85 neurons. In contrast, cumulatively deleting Dbxl XII premotor neurons decreased motor output monotonically but did not affect frequency nor stop XII output regardless of the ablation tally. Here, we couple an existing preBötC model with a premotor population in several topological configurations to investigate which one may replicate the laser ablation experiments best. If the XII premotor population is a "small-world" network (rich in local connections with sparse long-range connections among constituent premotor neurons) and connected with the preBötC such that the total number of incoming synapses remains fixed, then the in silico system successfully replicates the in vitro laser ablation experiments. This study proposes a feasible configuration for circuits consisting of Dbxl-derived interneurons that generate inspiratory rhythm and motor pattern. [ABSTRACT FROM AUTHOR]

Telomerase activation plays a critical role in human carcinogenesis through the maintenance of telomeres, but the activation mechanism during carcinogenesis remains unclear. The human telomerase reverse transcriptase (hTERT) promoter has been shown to promote hTERT gene expression selectively in tumor cells but not in normal cells. Deregulation of the Wnt/β- catenin signaling pathway is reported to be associated with human carcinogenesis. However, little is known about whether the Wnt/β-catenin pathway is involved in activating hTERT transcription and inducing telomerase activity (TA). In this study, we report that hTERT is a novel target of the Wnt/β- catenin pathway. Transient activation of the Wnt/β-catenin pathway either by transfection of a constitutively active form of β-catenin or by LiCl or Wnt-3a conditioned medium treatment induced hTERT mRNA expression and elevated TA in different cell lines. Furthermore, we found that silencing endogenous β-catenin expression by β-catenin gene-specific shRNA effectively decreased hTERT expression, suppressed TA, and accelerated telomere shortening. Of the four members of the lymphoid- enhancing factor (LEF)/T-cell factor (TCF) family, only TCF4 showed more effective stimulation on the hTERT promoter. Ectopic expression of a dominant negative form of TCF4 inhibited hTERT expression in cancer cells. Through promoter mapping, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, we found that hTERT is a direct target of β-catenin·TCF4-mediated transcription and that the TCF4 binding site at the hTERT promoter is critical for β-catenin·TCF4-dependent expression regulation. Given the pivotal role of telomerase in carcinogenesis, these results may offer insight into the regulation of telomerase in human cancer. [ABSTRACT FROM AUTHOR]