Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes

Many Commercially Available Antibodies for Detection of CHOP Expression as a Marker of Endoplasmic Reticulum Stress Fail Specificity Evaluation

Endoplasmic reticulum (ER) stress contributes to beta cell death in type 2 diabetes (T2DM). ER stress is characterized by increased level of ER stress markers such as C/EBP homologous protein (CHOP). Activation of CHOP leads to its translocation into the nucleus, where it induces cell death. We previously reported nuclear CHOP in pancreatic sections from T2DM, but not T1DM, and in human islet amyloid polypeptide (IAPP) transgenic rodent pancreatic sections. These studies underscore the importance of studying nuclear CHOP. We have observed inconsistency in the detection of CHOP antibodies reported in the literature and also in our own experiments. To investigate the specificity of CHOP antibodies, we first induced ER stress by tunicamycin in rat insulinoma (INS) cells and prepared nuclear and cytoplasmic fractions. Then we examined CHOP expression by Western blotting and immunocytochemistry using seven commercially available CHOP antibodies in INS cells and human IAPP (h-IAPP) transgenic rodent pancreatic tissue. These studies show that three commercially available CHOP antibodies out of seven tested were non-specific. In conclusion, we give recommendations for CHOP antibody selection and methods to verify CHOP antibody specificity. Also, we propose that the authors report the catalog and lot numbers of the CHOP antibodies used

Enabling effective tree exploration using visual cues

© 2018 Elsevier Ltd This article presents a new interactive visualization for exploring large hierarchical structures by providing visual cues on a node link tree visualization. Our technique provides topological previews of hidden substructures with three types of visual cues including simple cues, tree cues and treemap cues. We demonstrate the visual cues on Degree-of-Interest Tree (DOITree) due to its familiar mapping, its capability of providing multiple focused nodes, and its dynamic rescaling of substructures to fit the available space. We conducted a usability study with 28 participants that measured completion time and accuracy across five different topology search tasks. The simple cues had the fastest completion time across three of the node identification tasks. The treemap cues had the highest rate of correct answers on four of the five tasks, although only reaching statistical significance for two of these. As predicted, user ratings demonstrated a preference for the easy to understand tree cues followed by the simple cue, despite this not consistently reflected in performance results

Intranasal immunisation with Ag85B peptide 25 displayed on Lactococcus lactis using the PilVax platform induces antigen-specific B- and T-cell responses.

Mycobacterium tuberculosis (Mtb) remains a global epidemic despite the widespread use of BCG. Consequently, novel vaccines are required to facilitate a reduction in Mtb morbidity and mortality. PilVax is a peptide delivery strategy for the generation of highly specific mucosal immune responses and is based on the food-grade bacterium Lactococcus lactis that is used to express selected peptides engineered within the Streptococcus pyogenes M1T1 pilus, allowing for peptide amplification, stabilisation, and enhanced immunogenicity. In the present study, the dominant T cell epitope from the Mtb protein Ag85B was genetically engineered into the pilus backbone subunit and expressed on the surface of L. lactis. Western blot and flow cytometry confirmed formation of pilus containing the peptide DNA sequence. B cell responses in intranasally vaccinated mice were analysed by ELISA while T cell responses were analysed by flow cytometry. Serum titres of peptide specific IgG and IgA were detected, confirming vaccination produced antibodies against the cognate peptide. Peptide-specific IgA was also detected across several mucosal sites sampled. Peptide-specific CD4+ T cells were detected at levels similar to those of mice immunised with BCG. PilVax immunisation resulted in an unexpected increase in the numbers of CD3+ CD4- CD8- (double negative, DN) T cells in the lungs of vaccinated mice. Analysis of cytokine production following stimulation with the cognate peptide showed the major cytokine producing cells to be CD4+ T cells and DN T cells. This study provides insight into the antibody and peptide specific cellular immune responses generated by PilVax vaccination and demonstrates the suitability of this vaccine for conducting a protection study

Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage.

Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone

Two-dimensional amine and hydroxy functionalized fused aromatic covalent organic framework

Ordered two-dimensional covalent organic frameworks (COFs) have generally been synthesized using reversible reactions. It has been difficult to synthesize a similar degree of ordered COFs using irreversible reactions. Developing COFs with a fused aromatic ring system via an irreversible reaction is highly desirable but has remained a significant challenge. Here we demonstrate a COF that can be synthesized from organic building blocks via irreversible condensation (aromatization). The as-synthesized robust fused aromatic COF (F-COF) exhibits high crystallinity. Its lattice structure is characterized by scanning tunneling microscopy and X-ray diffraction pattern. Because of its fused aromatic ring system, the F-COF structure possesses high physiochemical stability, due to the absence of hydrolysable weak covalent bonds

Effect of nickel on the microstructure and mechanical property of die-cast Al–Mg–Si–Mn alloy

The effect of nickel on the microstructure and mechanical properties of a die-cast Al–Mg–Si–Mn alloy has been investigated. The results show that the presence of Ni in the alloy promotes the formation of Ni-rich intermetallics. These occur consistently during solidification in the die-cast Al–Mg–Si–Mn alloy across different levels of Ni content. The Ni-rich intermetallics exhibit dendritic morphology during the primary solidification and lamellar morphology during the eutectic solidification stage. Ni was found to be always associated with iron forming AlFeMnSiNi intermetallics, and no Al3Ni intermetallic was observed when Ni concentrations were up to 2.06 wt% in the alloy. Although with different morphologies, the Ni-rich intermetallics were identified as the same AlFeMnSiNi phase bearing a typical composition of Al[100–140](Fe,Mn)[2–7]SiNi[4–9]. With increasing Ni content, the spacing of the α-Al–Mg2Si eutectic phase was enlarged in the Al–Mg–Si–Mn alloy. The addition of Ni to the alloy resulted in a slight increase in the yield strength, but a significant decrease in the elongation. The ultimate tensile strength (UTS) increased slightly from 300 to 320 MPa when a small amount (e.g. 0.16 wt%) of Ni was added to the alloy, but further increase of the Ni content resulted in a decrease of the UTS.The Engineering and Physical Sciences Research Council (EPSRC), Technology Strategy Board (TSB) and Jaguar Land Rover (JLR) in the United Kingdom

Creating robust superamphiphobic coatings for both hard and soft materials

Most superhydrophobic surfaces lose their water-repellency when either contaminated by oily liquids or by being mechanically damaged. Superamphiphobic surfaces are ones that repel both oil and water. However, to date such surfaces are hampered by being mechanically weak. Robust superamphiphobic surfaces with highly water and oil repellent properties are desired for a wide range of environments. Reported herein is a superamphiphobic coatings fabricated by a facile deposition method and followed by a low surface energy materials modification. These coatings can be applied on both hard and soft materials to repel water, glycerol, peanut-oil droplets and some organic solvents. Falling sand abrasion, UV irradiation and aqueous media immersion were used to test the mechanical robustness and durability of the superamphiphobic coatings. A multi-cycle stretch/release test was developed to characterize the robustness of the self-cleaning soft materials. A coated rubber-bond retained both water and oil repellency even after 50 stretch/release cycles. These tests show that the superamphiphobic coatings have remarkable mechanical robustness and UV/aqueous media resistance and can be readily applied to a wide variety of materials to form self-cleaning surfaces that are extremely robust and durable even under intense strains

Power-free water pump based on a superhydrophobic surface: generation of a mushroom-like jet and anti-gravity long-distance transport

Spontaneous anti-gravitational transportation of liquids across long distances has been widely discovered in nature, such as water transportation from the root to the crown of a tree. However, artificial liquid delivery remains a challenge. In this work, a new power-free pump composed of a superhydrophobic plate with a pore mounted on a leak-proof cylindrical container filled with water is presented for sustained anti-gravity and long distance transport. Water droplets can be spontaneously captured through the pore by the lower water column, forming a mushroom-like jet due to the energy transition from surface energy to kinetic energy. The spontaneously increased inside pressure in the container will push the water out, through another thin tube, realizing the energy transition from surface energy to gravitational potential energy. The dynamic driving and moving model of the pivotal mushroom-like jet were analyzed. The maximum transport height and transport abilities of the water pump were also discussed. The results show that Laplace pressure is the main driving pressure of the mushroom-like jet and that the developed power-free pump can effectively transport water to over 100 mm in height with an average transport speed of 4500 μL h−1, showing potential for application in microfluidic systems and medical devices where micropumps are needed

Superfluid vs Ferromagnetic Behaviour in a Bose Gas of Spin-1/2 Atoms

We study the thermodynamic phases of a gas of spin-1/2 atoms in the Hartree-Fock approximation. Our main result is that, for repulsive or weakly-attractive inter-component interaction strength, the superfluid and ferromagnetic phase transitions occur at the same temperature. For strongly-attractive inter-component interaction strength, however, the ferromagnetic phase transition occurs at a higher temperature than the superfluid phase transition. We also find that the presence of a condensate acts as an effective magnetic field that polarizes the normal cloud. We finally comment on the validity of the Hartree-Fock approximation in describing different phenomena in this system.Comment: 10 pages, 2 figure