Co-existence of intact stemness and priming of neural differentiation programs in mES cells lacking Trim71.

Regulatory networks for differentiation and pluripotency in embryonic stem (ES) cells have long been suggested to be mutually exclusive. However, with the identification of many new components of these networks ranging from epigenetic, transcriptional, and translational to even post-translational mechanisms, the cellular states of pluripotency and early differentiation might not be strictly bi-modal, but differentiating stem cells appear to go through phases of simultaneous expression of stemness and differentiation genes. Translational regulators such as RNA binding proteins (RBPs) and micro RNAs (miRNAs) might be prime candidates for guiding a cell from pluripotency to differentiation.

Transcriptome assessment reveals a dominant role for TLR4 in the activation of human monocytes by the alarmin MRP8.

The alarmins myeloid-related protein (MRP)8 and MRP14 are the most prevalent cytoplasmic proteins in phagocytes. When released from activated or necrotic phagocytes, extracellular MRP8/MRP14 promote inflammation in many diseases, including infections, allergies, autoimmune diseases, rheumatoid arthritis, and inflammatory bowel disease. The involvement of TLR4 and the multiligand receptor for advanced glycation end products as receptors during MRP8-mediated effects on inflammation remains controversial.

Thyme oil nanoemulsions coemulsified by sodium caseinate and lecithin.

Many nanoemulsions are currently formulated with synthetic surfactants. The objective of the present work was to study the possibility of blending sodium caseinate (NaCas) and lecithin to prepare transparent thyme oil nanoemulsions. Thyme oil was emulsified using NaCas and soy lecithin individually or in combination at neutral pH by shear homogenization.

Regulatory roles of c-jun in H5N1 influenza virus replication and host inflammation.

The cytokine storm which is a great burden on humanity in highly pathogenic influenza virus infections requires activation of multiple signaling pathways. These pathways, such as MAPK and JNK, are important for viral replication and host inflammatory response. Here we examined the roles of JNK downstream molecule c-jun in host inflammatory responses and H5N1 virus replication using a c-jun targeted DNAzyme (Dz13).

Blending lecithin and gelatin improves the formation of thymol nanodispersions.

Delivery systems of lipophilic antimicrobials such as thymol prepared with generally recognized-as-safe ingredients are needed to enhance the microbiological safety of low-acid (pH > 4.6) foods. Nanodispersions with particle diameters below 100 nm are particularly demanded because of the low turbidity and physical stability.

Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.

Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization, and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a data set of 299 macrophage transcriptomes.

[The estrogen-like and antioxidant effects of pilose antler blood wine in female rats with ovariectomy].

Objective: To investigate whether pilose antler blood wine has the effects of estrogen-like activity and antioxidant in the ovariectomized (OVX) female rats.

Methods: The rat model of oxidative stress was established by ovariectomy. The female rats were divided into 6 groups: normal control group, OVX group, base wine group, and 3 pilose antler blood wine treated OVX groups (low, medium and high dose of wine at a dose of 4.

Self-presentation on the Web: agencies serving abused and assaulted women.

Objectives: We examined the content and usability of the Web sites of agencies serving women victims of violence.

Methods: We entered the names of a systematic 10% sample of 3774 agencies listed in 2 national directories into a search engine. We took (in April 2012) and analyzed screenshots of the 261 resulting home pages and the readability of 193 home and first-level pages.

Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus.

The ribonucleoprotein (RNP) of the influenza A virus is responsible for the transcription and replication of viral RNA in the nucleus. These processes require interplay between host factors and RNP components. Here, we report that the Fragile X mental retardation protein (FMRP) targets influenza virus RNA synthesis machinery and facilitates virus replication both in cell culture and in mice.

TRIM14 is a mitochondrial adaptor that facilitates retinoic acid-inducible gene-I-like receptor-mediated innate immune response.

Innate immunity provides the first line of host defense against invading microbial pathogens. This defense involves retinoic acid-inducible gene-I-like receptors that detect viral RNA and activate the mitochondrial antiviral-signaling (MAVS) protein, an adaptor protein, leading to activation of the innate antiviral immune response. The mechanisms by which the MAVS signalosome assembles on mitochondria are only partially understood.

Thymol nanoemulsified by whey protein-maltodextrin conjugates: the enhanced emulsifying capacity and antilisterial properties in milk by propylene glycol.

The objective of this research was to enhance the capability of whey protein isolate-maltodextrin conjugates in nanoemulsifying thymol using propylene glycol to improve antilisterial properties in milk. Thymol was predissolved in PG and emulsified in 7% conjugate solution. Transparent dispersions with mean diameters of <30 nm were observed up to 1.

Nizatidine, a small molecular compound, enhances killed H5N1 vaccine cell-mediated responses and protects mice from lethal viral challenge.

Nizatidine (NIZ), closely related to Cimetidine, is a histamine H2 receptor inverse agonist used primarily as an anti-acid drug. Recent studies showed that this class of compounds may also modulate immune responses. To evaluate adjuvant effects of NIZ on vaccine immune modulation, we formulated NIZ with a H5N1 killed viral antigen and tested in vitro and in vivo.

CD8+ Treg cells suppress CD8+ T cell-responses by IL-10-dependent mechanism during H5N1 influenza virus infection.

Although Treg-cell-mediated suppression during infection or autoimmunity has been described, functions of Treg cells during highly pathogenic avian influenza virus infection remain poorly characterized. Here we found that in Foxp3-GFP transgenic mice, CD8(+) Foxp3(+) Treg cells, but not CD4(+) Foxp3(+) Treg cells, were remarkably induced during H5N1 infection. In addition to expressing CD25, the CD8(+) Foxp3(+) Treg cells showed a high level of GITR and produced IL-10.

High-resolution transcriptome of human macrophages.

Macrophages are dynamic cells integrating signals from their microenvironment to develop specific functional responses. Although, microarray-based transcriptional profiling has established transcriptional reprogramming as an important mechanism for signal integration and cell function of macrophages, current knowledge on transcriptional regulation of human macrophages is far from complete. To discover novel marker genes, an area of great need particularly in human macrophage biology but also to generate a much more thorough transcriptome of human M1- and M1-like macrophages, we performed RNA sequencing (RNA-seq) of human macrophages.

Use of praziquantel as an adjuvant enhances protection and Tc-17 responses to killed H5N1 virus vaccine in mice.

Background: H5N1 is a highly pathogenic influenza A virus, which can cause severe illness or even death in humans. Although the widely used killed vaccines are able to provide some protection against infection via neutralizing antibodies, cytotoxic T-lymphocyte responses that are thought to eradicate viral infections are lacking.

Methodology/principal Findings: Aiming to promote cytotoxic responses against H5N1 infection, we extended our previous finding that praziquantel (PZQ) can act as an adjuvant to induce IL-17-producing CD8(+) T cells (Tc17).

Mast cell-induced lung injury in mice infected with H5N1 influenza virus.

Although an important role for mast cells in several viral infections has been demonstrated, its role in the invasion of highly pathogenic H5N1 influenza virus is unknown. In the present study, we demonstrate that mast cells were activated significantly by H5N1 virus (A/chicken/Henan/1/2004) infection both in vivo and in vitro. Mast cells could possibly intensify the lung injury that results from H5N1 infection by releasing proinflammatory mediators, including histamine, tryptase, and gamma interferon (IFN-γ).

Importance of MUC1 and spontaneous mouse tumor models for understanding the immunobiology of human adenocarcinomas.

Many important aspects of cancer biology, such as cancer initiation, progression, and metastasis, have been studied in animal models, mostly mice. As long as cancer was considered primarily a genetic disease, the study of transplantable mouse tumors, or even human tumor xenografts in immunocompromised mice, appeared to suffice. Many important genetic events that lead to transformation and in vivo tumor growth were elucidated.

Effect of high-voltage electrostatic field pretreatment on the antioxidant system in stored green mature tomatoes.

Background: High-voltage electrostatic field (HVEF), as a feasible and non-chemical technique, applied to food preservation is a new area of study. Our previous research suggested HVEF could maintain the quality of tomato in storage. The present article intensively investigated the effect of HVEF pretreatment on antioxidant system of green mature tomato in storage.

Inhibition of highly pathogenic avian H5N1 influenza virus propagation by RNA oligonucleotides targeting the PB2 gene in combination with celecoxib.

Background: Highly pathogenic avian influenza virus H5N1 can cause acute respiratory infections with an uncontrolled virus-induced cytokine storm in both poultry and humans. In view of the high mortality of H5N1 influenza virus infection, the development of novel broad-spectrum prophylactic and therapeutic agents against infection is urgently needed. In the present study, we attempted to explore whether the combinational use of a viral gene-targeted agent and immunomodulator is feasible as a new strategy against the H5N1 infection.

Synthesis 1-acyl-3-(2'-aminophenyl) thioureas as anti-intestinal nematode prodrugs.

A series of 1-acyl-3-(2'-aminophenyl) thiourea derivatives were designed and synthesized. The structures of all the newly synthesized compounds were identified by IR, elemental analysis, ¹H-NMR and ¹³C-NMR. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in rats by an oral route.

Generation of a tumor vaccine candidate based on conjugation of a MUC1 peptide to polyionic papillomavirus virus-like particles.

Virus-like particles (VLPs) are promising vaccine technology due to their safety and ability to elicit strong immune responses. Chimeric VLPs can extend this technology to low immunogenicity foreign antigens. However, insertion of foreign epitopes into the sequence of self-assembling proteins can have unpredictable effects on the assembly process.

Variations on the SnCl4 and CF3CO2Ag-promoted glycosidation of sugar acetates: a direct, versatile and apparently simple method with either alpha or beta stereocontrol.

Glycosidation of sugar peracetates (D-gluco, D-galacto) with SnCl(4) and CF(3)CO(2)Ag led to either 1,2-cis-, or 1,2-trans-glycosides, depending primarily on the alcohols used. In particular, 1,2-trans-glycosides, expected from acyl-protected glycosyl donors, were formed in high yields with alcohols sharing specific features such as bulkiness, presence of electron-withdrawing groups or polyethoxy motifs. In contrast, simple alcohols afforded approximately 1:1 mixtures of 2,3,4,6-tetra-O-acetyl, and 3,4,6-tri-O-acetyl 1,2-cis-glycosides due to anomerization and/or acid-catalyzed fragmentation of 1,2-orthoester intermediates.

G-CSF stimulates Jak2-dependent Gab2 phosphorylation leading to Erk1/2 activation and cell proliferation.

Granulocyte colony-stimulating factor (G-CSF), the major cytokine regulator of neutrophilic granulopoiesis, stimulates both the proliferation and differentiation of myeloid precursors. A variety of signaling proteins have been identified as mediators of G-CSF signaling, but understanding of their specific interactions and organization into signaling pathways for particular cellular effects is incomplete. The present study examined the role of the scaffolding protein Grb2-associated binding protein-2 (Gab2) in G-CSF signaling.

Src family tyrosine kinases are activated by Flt3 and are involved in the proliferative effects of leukemia-associated Flt3 mutations.

Objective: The hematopoietic growth factor receptor, Fms-like tyrosine kinase-3 (Flt3), modulates survival and proliferation of myeloid and B-cell precursors. Activating mutations of Flt3 are the most common molecular abnormalities in acute myeloid leukemia (AML) and have an apparent role in leukemogenesis. However, signaling pathways mediating Flt3 effects are incompletely understood.