Search

[Display omitted] • Four ciliate-specific subfamilies occurred during evolution of eukaryotic actin gene family. • Expansions of Act2 and ArpC might happen in the ciliate common ancestor. • Expansions of ActI and ActII may have occurred in the ancestor of three ciliate classes. • The number of actin isoforms varied greatly among ciliate species. • Actin gene family in ciliates went through "birth and death" evolution model. Actin gene family is a divergent and ancient eukaryotic cellular cytoskeletal gene family, and participates in many essential cellular processes. Ciliated protists offer us an excellent opportunity to investigate gene family evolution, since their gene families evolved faster in ciliates than in other eukaryotes. Nonetheless, actin gene family is well studied in few model ciliate species but little is known about its evolutionary patterns in ciliates. Here, we analyzed the evolutionary pattern of eukaryotic actin gene family based on genomes/transcriptomes of 36 species covering ten ciliate classes, as well as those of nine non-ciliate eukaryotic species. Results showed: (1) Except for conventional actins and actin-related proteins (Arps) shared by various eukaryotes, at least four ciliate-specific subfamilies occurred during evolution of actin gene family. Expansions of Act2 and ArpC were supposed to have happened in the ciliate common ancestor, while expansions of ActI and ActII may have occurred in the ancestor of Armophorea, Muranotrichea, and Spirotrichea. (2) The number of actin isoforms varied greatly among ciliate species. Environmental adaptability, whole genome duplication (WGD) or segmental duplication events, distinct spatial and temporal patterns of expression might play driving forces for the variation of isoform numbers. (3) The 'birth and death' model of evolution could explain the evolution of actin gene family in ciliates. And actin genes have been generally under strong negative selection to maintain protein structures and physiological functions. Collectively, we provided meaningful information for understanding the evolution of eukaryotic actin gene family. [ABSTRACT FROM AUTHOR]

Highlights: [•] Scene gist affects 15-month-olds, as it affects adults, when they detect changes. [•] Gist-preserving changes are easily missed despite being perceptually salient. [•] Gist-disrupting changes are readily detected despite being perceptually subtle. [•] Core physical knowledge may overpower scene gist to flag gist-preserving changes. [•] Once accessed, knowledge overrules perceptual cues in infants’ change detection. [Copyright &y& Elsevier]

Highlights: [•] From crayfish tissues cDNAs encoding CHH precursor were identified. [•] CHH2-L and CHH2 encode precursors containing classic CHH-like or CHH peptide. [•] tCHH2 expressed in hemocyte encodes a precursor containing a truncated CHH peptide. [•] CHH2-L, tCHH2, and CHH2 contain AU-rich elements in their 3′-untranslated regions. [ABSTRACT FROM AUTHOR]

Abstract: We previously described a putative role for inosine monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme in de novo guanine nucleotide biosynthesis, in lipid accumulation. Here we present data which demonstrate that IMPDH activity is required for differentiation of preadipocytes into mature, lipid-laden adipocytes and maintenance of adipose tissue mass. In 3T3-L1 preadipocytes inhibition of IMPDH with mycophenolic acid (MPA) reduced intracellular GTP levels by 60% (p <0.05) and blocked adipogenesis (p <0.05). Co-treatment with guanosine, a substrate in the salvage pathway of nucleotide biosynthesis, restored GTP levels and adipogenesis demonstrating the specificity of these effects. Treatment of diet-induced obese mice with mycophenolate mofetil (MMF), the prodrug of MPA, for 28days did not affect food intake or lean body mass but reduced body fat content (by 36%, p =0.002) and adipocyte size (p =0.03) and number. These data suggest that inhibition of IMPDH may represent a novel strategy to reduce adipose tissue mass. [Copyright &y& Elsevier]

Abstract: As they observe or produce events, infants identify variables that help them predict outcomes in each category of events. How do infants identify a new variable? An explanation-based learning (EBL) account suggests three essential steps: (1) observing contrastive outcomes relevant to the variable; (2) discovering the conditions associated with these outcomes; and (3) generating an explanation for the condition-outcome regularity discovered. In Experiments 1–3, 9-month-old infants watched events designed to “teach” them the variable height in covering events. After watching these events, designed in accord with the EBL account, the infants detected a height violation in a covering event, three months earlier than they ordinarily would have. In Experiments 4–6, the “teaching” events were modified to remove one of the EBL steps, and the infants no longer detected the height violation. The present findings thus support the EBL account and help specify the processes by which infants acquire their physical knowledge. [Copyright &y& Elsevier]

Abstract: In this paper, several existence theorems of positive solutions are established for nonlinear m-point boundary value problem for p-Laplacian dynamic equations on time scales, as an application, an example to demonstrate our results is given. The conditions we used in the paper are different from those in [H.R. Sun, W.T. Li, Positive solutions for nonlinear three-point boundary value problems on time scales, J. Math. Anal. Appl. 299 (2004) 508–524; H.R. Sun, W.T. Li, Positive solutions for nonlinear m-point boundary value problems on time scales, Acta Math. Sinica 49 (2006) 369–380 (in Chinese); Y. Wang, C. Hou, Existence of multiple positive solutions for one-dimensional p-Laplacian, J. Math. Anal. Appl. 315 (2006) 144–153; Y. Wang, W. Ge, Positive solutions for multipoint boundary value problems with one-dimensional p-Laplacian, Nonlinear Appl. 66 (6) (2007) 1246–1256]. [Copyright &y& Elsevier]

Abstract: Medical countermeasures to prevent or treat smallpox are needed due to the potential use of poxviruses as biological weapons. Safety concerns with the currently available smallpox vaccine indicate a need for research on alternative poxvirus vaccine strategies. Molecular vaccines involving the use of proteins and/or genes and recombinant antibodies are among the strategies under current investigation. The poxvirus L1 protein, encoded by the L1R open reading frame, is the target of neutralizing antibodies and has been successfully used as a component of both protein subunit and DNA vaccines. L1-specific monoclonal antibodies (e.g., mouse monoclonal antibody mAb-7D11, mAb-10F5) with potent neutralizing activity bind L1 in a conformation-specific manner. This suggests that proper folding of the L1 protein used in molecular vaccines will affect the production of neutralizing antibodies and protection. Here, we co-crystallized the Fab fragment of mAb-7D11 with the L1 protein. The crystal structure of the complex between Fab-7D11 and L1 reveals the basis for the conformation-specific binding as recognition of a discontinuous epitope containing two loops that are held together by a disulfide bond. The structure of this important conformational epitope of L1 will contribute to the development of molecular poxvirus vaccines and also provides a novel target for anti-poxvirus drugs. In addition, the sequence and structure of Fab-7D11 will contribute to the development of L1-targeted immunotherapeutics. [Copyright &y& Elsevier]

Abstract: Gene/protein interactions provide critical information for a thorough understanding of cellular processes. Recently, considerable interest and effort has been focused on the construction and analysis of genome-wide gene networks. The large body of biomedical literature is an important source of gene/protein interaction information. Recent advances in text mining tools have made it possible to automatically extract such documented interactions from free-text literature. In this paper, we propose a comprehensive framework for constructing and analyzing large-scale gene functional networks based on the gene/protein interactions extracted from biomedical literature repositories using text mining tools. Our proposed framework consists of analyses of the network topology, network topology–gene function relationship, and temporal network evolution to distill valuable information embedded in the gene functional interactions in the literature. We demonstrate the application of the proposed framework using a testbed of P53-related PubMed abstracts, which shows that the literature-based P53 networks exhibit small-world and scale-free properties. We also found that high degree genes in the literature-based networks have a high probability of appearing in the manually curated database and genes in the same pathway tend to form local clusters in our literature-based networks. Temporal analysis showed that genes interacting with many other genes tend to be involved in a large number of newly discovered interactions. [Copyright &y& Elsevier]

Abstract: In this paper, the global solutions of initial value problems for nonlinear second-order integro-differential equations of mixed type in Banach spaces are investigated. The existence and uniqueness of solutions and their iterative approximation are obtained by using Mönch fixed point theorem and new comparison results. The results presented here essentially improve, generalize and unify many well-known results. [Copyright &y& Elsevier]

Abstract: In this paper, we study the existence of positive solutions for the nonlinear four-point singular boundary value problem for higher-order with p-Laplacian operator. By using the fixed-point index theory, the existence of positive solution and many positive solutions for nonlinear singular boundary value problem with p-Laplacian operator are obtained. [Copyright &y& Elsevier]

Abstract: In this paper, we study the existence of countable many positive solutions for a class of nonlinear singular boundary value systems with p-Laplacian operator: where , , f, g are lower semi-continuous functions, has countable many singularities on , . By using the fixed-point theorem of cone expansion and compression of norm type, the existence of countable many positive solutions for nonlinear singular boundary value system with p-Laplacian operator are obtained. [Copyright &y& Elsevier]

A gene encoding a novel RhoGAP of 1146 amino acids was isolated from rat testis RNA. Analysis of this protein identified two conserved domains, a RhoGAP domain and an RA domain. Thus the gene was named RARhoGAP. The RhoGAP domain contained conserved residues critical for RhoGAP activity, suggesting this domain is involved in the down-regulation of Rho GTPases. The presence of the RA domain suggests that RARhoGAP also functions as an effector for Ras- or Ral-like GTPases. RT-PCR analysis showed the transcript was ubiquitous in extragonadal tissues; however, Northern analysis indicated highest expression was in the testis. Homologues of rat RARhoGAP were found in mouse and human and were found expressed in testis by nested RT-PCR. In situ hybridization confirmed the specific expression of RARhoGAP in differentiating male germ cells. We postulate that RARhoGAP may be involved in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. [Copyright &y& Elsevier]

• H 2 S reduced fibrosis of atrial cells induced by Ang II. • MiR-133a alleviated the fibrosis of atrial cells induced by Ang II. • MiR-133a was required to participate in the regulation of H 2 S on atrial fibrosis. • CTGF was the direct target of miR-133a to regulate atrial fibrosis. Atrial fibrillation (AF) is a common clinical arrhythmia and can cause a variety of complications. To study the therapeutic effect of H 2 S in atrial fibrosis and explore the important role of miR-133a, in vitro experiments in human atrial fibroblasts (HAFs) were conducted. The fibrosis in HAFs was induced by Ang II. The expression levels of miR-133a and CTGF in HAFs were examined by qRT-PCR. The proliferation and migration of HAFs were detected by CCK-8 and cell scratch assays. The protein expressions of CTGF, collagen I, collagen III and α-SMA were detected by western blotting. The dual-luciferase reporter gene was used to detect the interaction between miR-133a and CTGF. The proliferation and migration of HAFs stimulated by Ang II were enhanced, the expression of miR-133a was reduced, and the levels of CTGF and fibrosis markers (collagen I, collagen III and α-SMA) were increased. Furthermore, H 2 S reduced fibrosis, proliferation and migration of HAFs induced by Ang II. Accordingly, overexpression of miR-133a inhibited the proliferation and migration ability on Ang II-induced HAFs, and decreased the protein expressions of related fibrosis markers and CTGF. Meanwhile, miR-133a inhibitor could reverse the inhibition effect of H 2 S on proliferation and migration in HAFs by Ang II-induced. By targeting CTGF, miR-133a inhibited the expression of CTGF. H 2 S improved myocardial cell fibrosis by significantly increasing the expression of miR-133a, and CTGF might be a potential target for miR-133a to play an important role in myocardial fibrosis. [ABSTRACT FROM AUTHOR]

The foot-and-mouth disease virus capsid precursor, P1–2A, is cleaved by the 3C protease (3C pro ) to VP0, VP3, VP1 and 2A. The P1–2A precursor (wt or mutant) was expressed alone or with 3C pro and processing of P1–2A was determined. The VP2 K217R and VP3 I2P substitutions (near the VP0/VP3 junction) strongly reduced the processing at this junction by 3C pro while the substitution VP2 K217E blocked cleavage. At the VP3/VP1 junction, the substitutions VP3 Q2221P and VP1 T1P each severely inhibited processing at this site. Blocking cleavage at either junction did not prevent processing elsewhere in P1–2A. These modifications were also introduced into full-length FMDV RNA; only wt and the VP2 K217R mutant were viable. Uncleaved VP0-VP3 and the processed products were observed within cells infected with the mutant virus. The VP0-VP3 was not incorporated into empty capsids or virus particles. The three junctions within P1–2A are processed by 3C pro independently. [ABSTRACT FROM AUTHOR]

[Display omitted] • Phylogenomic trees covering all armophorean orders were generated for the first time. • Phylogenomic trees revealed Armophorida as an armophorean order or a new APM class. • The last common ancestor of APM should be an anaerobic free-living ciliate species. • Molecular and morphological evidences support non-monophyly of family Metopidae. Ciliate species within the class Armophorea are widely distributed in various anaerobic environments, hence they are of great interest to researchers studying evolution and adaptation of eukaryotes to extreme habitats. However, phylogenetic relationships within the class remain largely elusive, most especially assignment of the order Armophorida and classification within the family Metopidae. In this study, we newly sequenced transcriptomes and the SSU rDNA of five armophorean species, Sulfonecta cf. uniserialis (order Armophorida), Nyctotheroides sp. (order Clevelandellida), and Metopus major , M. paraes , and Brachonella contorta (order Metopida). Comprehensive phylogenomic analyses revealed that Armophorea was most closely related to Muranotrichea and Parablepharismea. Our results indicate that the order Armophorida either belongs to Armophorea or represents a new class within APM (Armophorea-Parablepharismea-Muranotrichea). Analyses combining ecological niches and molecular trees showed that APM species might descend from an anaerobic free-living ciliate species. Existing molecular phylogenomic/phylogenetic and morphological evidence indicate that the family Metopidae is non-monophyletic and should be further classified with inclusion of additional lines of evidences. Our results provide new insights into the long-debated relationships within Armophorea. [ABSTRACT FROM AUTHOR]

Autophagy is a double-edged sword that affects tumor progression by promoting cell survival or death depending on different living contexts. The concrete mechanism by which autophagy modulates the efficacy of radiotherapy for prostate cancer (PC) remains unclear. We exposed RM-1 PC cells to X-ray and explored the role of autophagy in radiation injury. Our results showed increased apoptosis and autophagy levels in RM-1 cells after radiation. Pharmacological inhibition of autophagy by chloroquine significantly mitigated radiation-induced apoptosis, while the enhancement of autophagy by rapamycin aggravated apoptosis. Sirt1, a member of sirtuin family, deacetylates various transcription factors to trigger cell survival in response to radiation injury. We found that radiation led to Sirt1 downregulation, which was reversed by the inhibition of autophagy. On the contrary, enhanced autophagy further diminished protein level of Sirt1. Notably, overexpression of Sirt1 by plasmid significantly alleviated radiation-induced apoptosis, but silenced Sirt1 by siRNA further induced apoptosis, indicating the radioprotective effect of Sirt1 on RM-1 cells. In summary, our findings suggested that autophagy-mediated Sirt1 downregulation might be a promising therapeutic target for PC. • The radiosensitivity of RM-1 prostate cancer cells is dose-dependent. • Autophagy-mediated Sirt1 downregulation causes apoptosis in irradiated RM-1 cells. • There exists an autophagy-Sirt1-apoptosis signaling axis in irradiated RM-1 cells. • Targeting autophagy and Sirt1 may be a potential therapeutic strategy for prostate cancer. [ABSTRACT FROM AUTHOR]

One Health is a collaborative, multi-sectoral, trans-disciplinary approach with the goal of achieving optimal health outcomes by recognizing the interconnection between people, animals, plants, and the environment and determining how this relates to the control of infectious diseases such as malaria, schistosomiasis and so on. Malarias caused by Plasmodium that commonly infects female Anopheles mosquitoes, which feed on human blood and act as a disease vector. It has been a worldwide important public health problem from ancient times. Also, malaria is one of the infectious diseases with the longest epidemic time and the most serious harm in the history of Henan Province, China. During the past decades, the multi-sectoral, cross-regional, and multi-disciplinary One Health approach contributed to a significant reduction in malaria incidence, resulting in initiation of the Henan Malaria Elimination Action Plan. Herein, we reviewed the history of the fight against malaria in Henan Province. A full picture of malaria epidemics, prevention, and control strategies were showed, with the objective that it will help stakeholders, and policy-makers to take informed decisions on public health issues and intervention designs on malaria control towards elimination in the similar areas. [ABSTRACT FROM AUTHOR]

Abstract: Nipah virus (NiV), a member of the Paramyxoviridae family, causes deadly encephalitis in humans and huge economic losses to the pig industry. Here, we generated recombinant avirulent Newcastle disease virus (NDV) LaSota strains expressing the NiV G and F proteins respectively (designated as rLa-NiVG and rLa-NiVF), and evaluated their immunogenicity in mice and pigs. Both rLa-NiVG and rLa-NiVF displayed growth properties similar to those of LaSota virus in chicken eggs. Co-infection of rLa-NiVG and rLa-NiVF caused marked syncytia formation, while intracerebral co-inoculation of these viruses in mice showed they were safe in at least one mammalian species. Animal immunization studies showed rLa-NiVG and rLa-NiVF induced NiV neutralizing antibody responses in mice and pigs, and F protein-specific CD8+ T cell responses in mice. Most importantly, rLa-NiVG and rLa-NiVF administered alone or together, induced a long-lasting neutralizing antibody response in pigs. Recombinant rLa-NiVG/F thus appear to be promising NiV vaccine candidates for pigs and potentially humans. [Copyright &y& Elsevier]

Abstract: Half-metallic Fe3O4 films grown on a Si (100) substrate with a tantalum (Ta) buffer layer were prepared by DC magnetron reactive sputtering. Primary emphasis was placed on magnetic field growth of Fe3O4 thin film. The experiment''s results showed that applying an external magnetic field to the samples during the growth was efficient to promote the polycrystalline Fe3O4 growth along certain directions. The magnetoresistance (MR) was also tested for comparison of the samples prepared with and without an external magnetic field, and showed that applying an external magnetic field can promote the MR values. [Copyright &y& Elsevier]

The baculovirus expression system is a powerful and widely used method to generate large quantities of recombinant protein. However, challenges exist in workflows utilizing either liquid baculovirus stocks or the Titerless Infected-Cells Preservation and Scale-Up (TIPS) method, including the time and effort to generate baculoviruses, screen for protein expression and store large numbers of baculovirus stocks. To mitigate these challenges, we have developed a streamlined, hybrid workflow which utilizes high titer liquid virus stocks for rapid plate-based protein expression screening, followed by a TIPS-based scale-up for larger protein production efforts. Additionally, we have automated each step in this screening workflow using a custom robotic system. With these process improvements, we have significantly reduced the time, effort and resources required to manage large baculovirus generation and expression screening campaigns. [ABSTRACT FROM AUTHOR]

Early repolarization syndrome (ERS) is defined as occurring in patients with early repolarization pattern who have survived idiopathic ventricular fibrillation with clinical evaluation unrevealing for other explanations. The pathophysiologic basis of the ERS is currently uncertain. The objective of the present study was to examine the electrophysiological mechanism of ERS utilizing induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing. Whole genome sequencing was used to identify the DPP6 (c.2561T > C/p.L854P) variant in four families with sudden cardiac arrest induced by ERS. Cardiomyocytes were generated from iPSCs from a 14-year-old boy in the four families with ERS and an unrelated healthy control subject. Patch clamp recordings revealed more significant prolongation of the action potential duration (APD) and increased transient outward potassium current (I to) (103.97 ± 18.73 pA/pF vs 44.36 ± 16.54 pA/pF at +70 mV, P < 0.05) in ERS cardiomyocytes compared with control cardiomyocytes. Of note, the selective correction of the causal variant in iPSC-derived cardiomyocytes using CRISPR/Cas9 gene editing normalized the I to , whereas prolongation of the APD remained unchanged. ERS cardiomyocytes carrying DPP6 mutation increased I to and lengthen APD, which maybe lay the electrophysiological foundation of ERS. [ABSTRACT FROM AUTHOR]

Abstract Nobiletin has protective effects on cardiovascular diseases, but the mechanism is not clear. In this study, we examined whether nobiletin affects the expression of miR-590/LPL and its relative effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. RT-qPCR analysis showed that nobiletin increased the expression of miR-590. Western blot analysis showed that nobiletin-suppressed LPL expression was enhanced by miR-590 mimic and abrogated by miR-590 inhibitor. Oil Red O staining and high-performance liquid chromatography assays showed that nobiletin attenuated lipid accumulation in macrophages. Treatment with nobiletin and miR-590 mimic decreased cellular lipid accumulation, whereas treatment with miR-590 inhibitor increased cellular lipid accumulation. ELISA illustrated that nobiletin alleviated pro-inflammatory cytokine secretion in macrophages as measured by, which was reduced by miR-590 mimic and increased by miR-590 inhibitor. In conclusion, nobiletin may alleviate lipid accumulation and secretion of pro-inflammatory cytokines by enhancing the inhibitory effect of miR-590 on LPL expression, suggesting a promising strategy for potential drug development for atherosclerosis. Highlights • Nobiletin may alleviate lipid accumulation in human THP-1 macrophages. • Nobiletin may alleviate secretion of pro-inflammatory cytokines in human THP-1 macrophages. • Nobiletin may enhance the inhibitory effect of miR-590 on LPL expression. [ABSTRACT FROM AUTHOR]

Objective We investigated the effect of topotecan on injury and inflammation in a model of ventilator-induced lung injury (VILI). Methods Acute lung injury (ALI) was induced in mice by high-tidal volume ventilation, and the mice were then treated with topotecan or PBS. Lung tissue and bronchoalveolar lavage fluid were collected to assess pulmonary vascular leaks, inflammation, and cell apoptosis. Results Compared to PBS treatment, topotecan significantly decreased the ALI score, myeloperoxidase (MPO) content, total protein concentration, and presence of inflammatory cells and inflammatory cytokines in bronchoalveolar lavage fluid. Topotecan also reduced caspase-3 activation and type Ⅱ alveolar epithelial cell apoptosis. Moreover, topotecan inhibited NF-κB expression and activation in the VILI model. Conclusion Topotecan alleviates acute lung injury in the model of VILI through the inhibition of the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Background Recent studies have revealed that mutation in KCNE1, β-subunits of cardiac potassium channel, involved in ventricular fibrillation. Whereas its role in early repolarization syndrome (ERS) is less well understood. Objective To study whether mutant in KCNE1 is associated with ERS and explore the possible underlying molecular mechanisms. Methods Whole genome from four unrelated families with ERS was amplified and sequenced. Wild-type (WT) KCNE1 and/or KCNE1-S38G (S38G) were expressed in HEK293 cells with KCNQ1. Functional studies included whole-cell patch-clamp, western blot and immunofluorescence were performed to reveal the possible underlying mechanisms. Results The co-expression of KCNE1-S38G and KCNQ1 decreased tail current density of I Ks but had little effect in modulation channel kinetics of I Ks . Compared with KCNE1-WT, the expression and membrane location of KCNE1-S38G decreased. Co-expression of KCNE1-WT and KCNE1-S38G partially rescued the function of I Ks channel. Conclusions The S38G mutation induced a loss-of-function of I Ks due to decreasing of KCNE1 protein expression and defecting in KCNE1 protein membrane trafficking. Our findings suggested that KCNE1 may be one of the possible modulatory genes associated to ERS. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate effects of dietary Lactobacillus delbrueckii ( L. delbrueckii ) on immune response, disease resistance against Aeromonas hydrophila ( A. hydrophila ), antioxidant capability and growth performance of Cyprinus carpio Huanghe var. 450 fish (mean weight of 1.05 ± 0.03 g) were randomly distributed into five groups that fed diets containing different levels of L. delbrueckii (0, 1 × 10 5 , 1 × 10 6 , 1 × 10 7 and 1 × 10 8 CFU g −1 ) for 8 weeks. The results showed that intestinal immune parameters such as lysozyme, acid phosphatase, and myeloperoxidase activities, immunoglobulin M content, and the survival rate were improved in fish fed with 1 × 10 6 and 1 × 10 7 CFU g −1 L. delbrueckii . In addition, 1 × 10 7 CFU g −1 L. delbrueckii supplementation down-regulated mRNA levels of TNF-α, IL-8, IL-1β and NF-κBp65, and up-regulated IL-10 and TGF-β mRNA levels in the intestine. The survival rate was significantly ( P < 0.05) higher (68.33%) in fish fed 1 × 10 6 CFU g −1 L. delbrueckii than the control diet-fed group (40%) after challenge by A. hydrophila. Fish fed with diet containing 1 × 10 6 CFU g −1 L. delbrueckii showed higher antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and total antioxidant capacity (T-AOC) and lower MDA concentrations than those of the control group ( P < 0.05). The relative gene expression (SOD, CAT, GPX) showed the same trend with their activities. In addition, the growth performance was significantly improved in fish fed with the diet containing 1 × 10 6 and 1 × 10 7 CFU g −1 L. delbrueckii ( P < 0.05). These results demonstrated that dietary optimal levels of L. delbrueckii enhanced immunity, disease resistance against A. hydrophila antioxidant capability and growth performance in Cyprinus carpio Huanghe var. [ABSTRACT FROM AUTHOR]

In this work, the MgAl 2-x (Cu 0.5 Ti 0.5) x O 4 (x ​= ​0, 0.04, 0.08, 0.12, 0.16, and 0.20) ceramic system was synthesized using the solid-state route. The crystalline phases, crystal structure,and microwave dielectric properties of the samples were investigated. The XRD data presented a typical spinel structure of MgAl 2 O 4 and was processed using the Rietveld refinement method. TiO 2 , Al 2 TiO 5 and MgTi 2 O 5 were considered as secondary phases. SEM indicated that the densification was affected by the (Cu 0.5 Ti 0.5)3+ content and sintering temperature. The successful fabrication of MgAl 2-x (Cu 0.5 Ti 0.5) x O 4 and the presence of MgTi 2 O 5 were confirmed by EDS. The densification, secondary phases and cation vacancies were responsible for the variation of Qf values. The ε r values were dominated by secondary phases and ionic polarizability. Meanwhile, secondary phases and bond valence had a significant influence on the τ f values. The optimum microwave dielectric properties (Qf ​= ​42,036 ​GHz, ε r ​= ​8.72 and τ f ​= ​-5.0 ​ppm/°C) were obtained. Temperature stability was improved by 93.8% when compared to pure MgAl 2 O 4 (τ f ​= ​-80.0 ​ppm/°C). The as-prepared ceramics possess low transmission delay time, high temperature stability, preferable frequency selective characteristics, and low dielectric loss. Near-zero temperature coefficient of resonance frequency with low permittivity of MgAl2-x(Cu0.5Ti0.5)xO4 ceramics. [Display omitted] • The near-zero τ f value (-5.0 ​ppm/°C) with low ε r (8.72) was obtained. • The microwave dielectric properties were improved via (Cu 0.5 Ti 0.5)3+ co-substituted for Al3+ in MgAl 2 O 4. • The co-substitution method can be applied to other materials. • This ceramic has low transmission delay time, high stability, frequency selectivity, and low dielectric loss. [ABSTRACT FROM AUTHOR]

The purpose of this study is to determine whether IL-27 regulates macrophage ABCA1 expression, foam cell formation, and also explore the underlying mechanisms. Here, we revealed that IL-27 decreased lipid accumulation in THP-1 derived macrophages through markedly enhancing cholesterol efflux and increasing ABCA1 expression at both protein and mRNA levels. Our study further demonstrated that IL-27 increased ABCA1 level via activation of signal transducer and activator of transcription 3 (STAT3). Inhibition of Janus kinase 2, (JAK2)/STAT3 suppressed the stimulatory effects of IL-27 on ABCA1 expression. The present study concluded that IL-27 reduces lipid accumulation of foam cell by upregulating ABCA1 expression via JAK2/STAT3. Therefore, targeting IL-27 may offer a promising strategy to treat atherosclerotic vascular disease. [ABSTRACT FROM AUTHOR]

Abstract: Apart from its role in axon guidance, netrin-1 is also known to be pro-angiogenic. The aim of this study is to determine whether adeno-associated viral (AAV) mediated overexpression of netrin-1 improves post-stroke neurovascular structure and recovery of function. AAV-Netrin-1 or AAV-LacZ of 1×1010 genome copies each was injected medial and posterior to ischemic lesion at one hour following reperfusion using the distal middle cerebral artery occlusion (MCAO) method. Quantitative RT-PCR revealed that the expression of netrin-1 transgene began as early as one day and increased dramatically about 3weeks following vector injection. Western blot analysis and confocal microscopy suggested that both the endogenous and transduced netrin-1 were expressed in the neurons of the peri-infarct cortex after MCAO. AAV-mediated netrin-1 overexpression significantly increased vascular density in the peri-infarct cortex and promoted the migration of immature neurons into the peri-infarct white matter, but it did not significantly reduce infarct size. Netrin-1 overexpression also enhanced post-stroke locomotor activity, improved exploratory behavior, and reduced ischemia-induced motor asymmetry in forelimb usage. However, it had little effect on post-stroke spatial learning and memory. Our results suggest that AAV mediated netrin-1 overexpression improves peri-infarct vascular density and post stroke motor function. [Copyright &y& Elsevier]

Abstract: Emodin—a major component of Rheum palmatum L.—exerts antiproliferative effects in cancer cells that are regulated by different signaling pathways. Hepatocellular carcinoma has high-incidence rates and is associated with poor prognosis and high mortality rates. This study was designed to evaluate the effects of emodin on human hepatocarcinoma cell viability and investigate its mechanisms of action in Huh7, Hep3B, and HepG2 cells. To define the molecular changes associated with this process, expression profiles were compared in emodin-treated hepatoma cells by cDNA microarray hybridization, quantitative RT-PCRs, and Western blot analysis. G2/M phase arrest was observed in all 3 cell lines. Cell cycle regulatory gene analysis showed increased protein levels of cyclin A, cyclin B, Chk2, Cdk2, and P27 in hepatoma cells after time courses of emodin treatment, and Western blot analysis showed decreased protein levels of Cdc25c and P21. Microarray expression profile data and quantitative PCR revealed that 15 representative genes were associated with emodin treatment response in hepatoma cell lines. The RNA expression levels of CYP1A1, CYP1B1, GDF15, SERPINE1, SOS1, RASD1, and MRAS were upregulated and those of NR1H4, PALMD, and TXNIP were downregulated in all three hepatoma cells. Moreover, at 6h after emodin treatment, the levels of GDF15, CYP1A1, CYP1B1, and CYR61 were upregulated. Here, we show that emodin treatment caused G2/M arrest in liver cancer cells and increased the expression levels of various genes both in mRNA and protein level. It is likely that these genes act as biomarkers for hepatocellular carcinoma therapy. [Copyright &y& Elsevier]

Abstract: Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16INK, p21 and p19ARF. VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI. [Copyright &y& Elsevier]

TREM2 has been identified by genomic analysis as a potential and novel target for the treatment of Alzheimer's disease. To enable structure-based screening of potential small molecule therapeutics, we sought to develop a robust crystallization platform for the TREM2 Ig-like domain. A systematic set of constructs containing the structural chaperone, maltose binding protein (MBP), fused to the Ig domain of TREM2, were evaluated in parallel expression and purification, followed by crystallization studies. Using protein crystallization and high-resolution diffraction as a readout, a MBP-TREM2 Ig fusion construct was identified that generates reproducible protein crystals diffracting at 2.0 Å, which makes it suitable for soaking of potential ligands. Importantly, analysis of crystal packing interfaces indicates that most of the surface of the TREM2 Ig domain is available for small molecule binding. A proof of concept co-crystallization study with a small library of fragments validated potential utility of this system for the discovery of new TREM2 therapeutics. • TREM2 genetic variants are associated with Alzheimer disease and Nasu-Hakola disease. • Molecules that modulate TREM2 signaling may lead to therapies for Alzheimer disease. • TREM2 crystallization system developed using an MBP fusion as structural chaperone. • Robust crystallization system could support small molecule screening campaigns. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that variants in dipeptidyl aminopeptidase-like protein-6 (DPP6) are involved in idiopathic ventricular fibrillation. However, its role in early repolarization syndrome (ERS) remains largely elusive. The aim of this study is to determine whether the novel DPP6-L747P variant is associated with ERS, and explore the underlying mechanisms. In our study, whole genome sequencing was used to identify a genetic variant in 4 Chinese families with sudden cardiac arrest induced by ERS. Then, wild-type (WT) DPP6 or mutant (c.2240T > C/p.L747P) DPP6 were respectively expressed in HEK293 cells, co-expressed with K V 4.3 and KChIP2. Western blotting, immunofluorescence, and whole-cell patch clamp experiments were performed to reveal possible underlying mechanisms. A novel missense variant (c.2240T > C/p.L747P) in DPP6 was identified in the 4 families. Both DPP6-WT and DPP6-L747P were mainly located on the cell membrane. Compared with DPP6-WT , the intensity of DPP6 protein bands was downregulated in DPP6-L747P. Functional experiments showed that macroscopic currents exhibited an increase in DPP6-L747P , and the current intensity of DPP6-L747P was increased more than that of DPP6-WT (63.1 ± 8.2 pA/pF vs.86.5 ± 15.1 pA/pF at +50 mV, P < 0.05). Compared with DPP6-WT , the slope of the activation curve of DPP6-L747P was slightly decreased (15.49 ± 0.56 mV vs. 13.88 ± 0.54 mV, P < 0.05), the slope of the inactivation curve was increased (13.65 ± 1.57 mV, vs. 24.44 ± 2.79 mV, P < 0.05) and the recovery time constant was significantly reduced (216.81 ± 18.59 ms vs. 102.11 ± 32.03 ms, P < 0.05). In conclusion, we identified a novel missense variant (c.2240T > C/p. L747P) in DPP6 in 4 Chinese families with sudden cardiac arrest induced by ERS. Patch clamp experiments revealed that this variant could generate a gain of function of I to and affect the potassium current. These results demonstrated that changes caused by the variant may be the underlying mechanisms of malignant arrhythmias in the individuals with ERS. [ABSTRACT FROM AUTHOR]