Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial complex I inhibition is not required for dopaminergic neuron death induced by rotenone, MPP+, or paraquat

Inhibition of mitochondrial complex I is one of the leading hypotheses for dopaminergic neuron death associated with Parkinson's disease (PD). To test this hypothesis genetically, we used a mouse strain lacking functional Ndufs4, a gene encoding a subunit required for complete assembly and function of complex I. Deletion of the Ndufs4 gene abolished complex I activity in midbrain mesencephalic neurons cultured from embryonic day (E) 14 mice, but did not affect the survival of dopaminergic neurons in culture. Although dopaminergic neurons were more sensitive than other neurons in these cultures to cell death induced by rotenone, MPP+, or paraquat treatments, the absence of complex I activity did not protect the dopaminergic neurons, as would be expected if these compounds act by inhibiting complex 1. In fact, the dopaminergic neurons were more sensitive to rotenone. These data suggest that dopaminergic neuron death induced by treatment with rotenone, MPP+, or paraquat is independent of complex I inhibition.
England's legislation on smoking in indoor public places and work-places: impact on the most exposed children.

AIMS To examine whether English legislation to make virtually all indoor public places and work-places smoke-free on 1 July 2007 displaced smoking into the home and hence increased the proportion of children exposed to levels of second-hand smoke known to be detrimental to health. DESIGN Repeated cross-sectional study with data from 10 annual surveys undertaken from 1996 to 2008. SETTING England. PARTICIPANTS Nationally representative samples of non-smoking children aged 4-15 years old living in private households. MEASUREMENTS Salivary cotinine, parental smoking status, whether smoking is allowed within the house, socio-demographic variables. FINDINGS The proportion of children exposed to damaging levels of second-hand smoke (defined as those with cotinine levels >1.7 ng/ml) has fallen over time, from 23.5% in 1996 to 12.6% in 2008. The legislation was not associated with further changes in the proportion of children above this threshold-the odds of having cotinine >1.7 ng/ml did not change after adjustment for the pre-legislative trend and confounders (odds ratio: 1.0, 95% confidence interval: 0.78, 1.4). Non-significant associations were also found when examining children by parental or household smoking status. CONCLUSIONS Legislation to prohibit smoking in indoor public places and work-places does not increase the proportion of children exposed to damaging levels of second-hand smoke. Even in a country with a strong tobacco control climate, a significant proportion of children remain highly exposed to second-hand smoke and future policies need to include interventions to reduce exposure among these children.
The “Cheshire Cat” escape strategy of the coccolithophore Emiliania huxleyi in response to viral infection

The coccolithophore Emiliania huxleyi is one of the most successful eukaryotes in modern oceans. The two phases in its haplodiploid life cycle exhibit radically different phenotypes. The diploid calcified phase forms extensive blooms, which profoundly impact global biogeochemical equilibria. By contrast, the ecological role of the noncalcified haploid phase has been completely overlooked. Giant phycodnaviruses (Emiliania huxleyi viruses, EhVs) have been shown to infect and lyse diploid-phase cells and to be heavily implicated in the regulation of populations and the termination of blooms. Here, we demonstrate that the haploid phase of E. huxleyi is unrecognizable and therefore resistant to EhVs that kill the diploid phase. We further show that exposure of diploid E. huxleyi to EhVs induces transition to the haploid phase. Thus we have clearly demonstrated a drastic difference in viral susceptibility between life cycle stages with different ploidy levels in a unicellular eukaryote. Resistance of the haploid phase of E. huxleyi provides an escape mechanism that involves separation of meiosis from sexual fusion in time, thus ensuring that genes of dominant diploid clones are passed on to the next generation in a virus-free environment. These “Cheshire Cat” ecological dynamics release host evolution from pathogen pressure and thus can be seen as an opposite force to a classic “Red Queen” coevolutionary arms race. In E. huxleyi, this phenomenon can account for the fact that the selective balance is tilted toward the boom-and-bust scenario of optimization of both growth rates of calcifying E. huxleyi cells and infectivity of EhVs.
DNA variation and symbiotic associations in phenotypically diverse sea urchin Strongylocentrotus intermedius

Strongylocentrotus intermedius (A. Agassiz, 1863) is an economically important sea urchin inhabiting the northwest Pacific region of Asia. The northern Primorye (Sea of Japan) populations of S. intermedius consist of two sympatric morphological forms, “usual” (U) and “gray” (G). The two forms are significantly different in morphology and preferred bathymetric distribution, the G form prevailing in deeper-water settlements. We have analyzed the genetic composition of the S. intermedius forms using the nucleotide sequences of the mitochondrial gene encoding the cytochrome c oxidase subunit I and the nuclear gene encoding bindin to evaluate the possibility of cryptic species within S. intermedius. We have examined the presence of symbiont microorganisms by means of 16S rRNA sequences. The nucleotide sequence divergence between the morphological forms is low: 0.74% and 0.70% for cytochrome c oxidase subunit I and nuclear gene encoding bindin, respectively, which is significantly below average intrageneric sequence divergence among Strongylocentrotus species. We thus have found no genetic evidence of cryptic species within S. intermedius. Phylogenetic analysis shows that the bacteria symbionts of S. intermedius belong to the phylum Bacteroidetes, but the U and G forms predominantly harbor highly divergent bacterial lineages belonging to two different taxonomic classes, Flavobacteria and Sphingobacteria. We propose that the U and G forms of S. intermedius represent distinct ecomorphological adaptations to contrasting shallow- and deep-water marine environments and might be considered incipient species. We also propose that the symbiotic bacteria likely play an important role in the evolution of morphological divergence of S. intermedius.
Social media guidance, designed by students for students, is well-received and may prompt changes in online behaviour

Social media offers opportunities to network and build a positive online profile; however, there is growing evidence that used unwisely, such sites can blur the lines between the personal and professional (Devi 2011) resulting in unanticipated negative consequences. In response to this, a number of health professional bodies have generated social media guidance for their members. Examination of this guidance reveals a range of content and formats. There is currently a paucity of research into healthcare students’ views on available guidance. The paper reports on an investigation of healthcare students’ views regarding currently existing social media guidance, the development of a new guide, that can be used by any healthcare student group (uni or multi professional) and commentary on the value of a student lead research project which results in a learning resource, developed by students, for students.
Strain‐Mediated Phase Control and Electrolyte‐Gating of Electron‐Doped Manganites

A prototype Mott transistor, the electric double layer transistor with a strained CaMnO(3) thin film, is fabricated. As predicted by the strain phase diagram of electron-doped manganite films, the device with the compressively strained CaMnO(3) exhibits an immense conductivity modulation upon applying a tiny gate voltage of 2 V.
Enhanced Photoelectrochemical Activity of the TiO2/ITO Nanocomposites Grown onto Single‐Walled Carbon Nanotubes at a Low Temperature by Nanocluster Deposition

High-resolution transmission electron microscopy (HRTEM) is used to observe a TiO2/ITO-coated composite nanostructure grown onto single-walled carbon nanotubes (SWCNTs). The SWCNTs, indium tin oxide (ITO), and TiO2 mixtures of anatase (A) and rutile (R) are clearly distinguished in the HRTEM images. The thickness of the SWCNT was about 3 nm, and the TiO2 shell included different polycrystalline structures.
Efficient Small Molecule Bulk Heterojunction Solar Cells with High Fill Factors via Pyrene‐Directed Molecular Self‐Assembly

Efficient organic photovoltaic (OPV) materials are constructed by attaching completely planar, symmetric end-groups to donor-acceptor electroactive small molecules. Appending C2-pyrene as the small molecule end-group to a diketopyrrolopyrrole core leads to materials with a tight, aligned crystal packing and favorable morphology dictated by π-π interactions, resulting in high power conversion efficiencies and high fill factors. The use of end-groups to direct molecular self-assembly is an effective strategy for designing high-performance small molecule OPV devices.
The influence of running and cycling on subsequent maximal muscular performance

BACKGROUND AND OBJECTIVE: The extent to which moderate intensity running or cycling impact subsequent maximal neuromuscular performance is unclear. Thus, the aim of the present study was to evaluate the effect of moderate intensity and volume running and cycling on maximal and explosive muscle strength. METHODS: Ten young physically active men were recruited and had their knee extension isometric peak torque, rate of torque development (RTD), and counter movement jump height measured at a baseline reference condition (REF) and after moderate intensity 30 min running (RUN) or cycling (CYC). Electromyographic activity of the quadriceps muscles was obtained during the isometric tests. RESULTS: No significant differences were found between conditions for isometric peak torque ( p> 0.05), RTD ( p> 0.05), countermovement jump ( p> 0.05), and the electromyographic amplitude ( p> 0.05). CONCLUSION: The present data indicate that maximal and explosive lower limb muscle strength is not compromised after 30 minutes of moderate intensity continuous exercise, independent of the mode of the exercise performed.
Metal–Polymer–Metal Split‐Dipole Nanoantennas

The conjugated polymer semiconductor poly(3-hexylthiophene), (P3HT), is integrated directly into the slot region of resonant plasmonic split-dipole nanoantennas. The P3HT radiative emission rate is enhanced by a factor of up to 29, in experiment, and 550 for the ideal case, due to the large local density of optical states in the nanoantenna slot region. Additionally, the theoretical modified luminescence quantum efficiency is shown to increase from 1% to 45% for optimized nanoantenna parameters.
Odor coding by modules of coherent mitral/tufted cells in the vertebrate olfactory bulb

Odor representation in the olfactory bulb (OB) undergoes a transformation from a combinatorial glomerular map to a distributed mitral/tufted (M/T) cell code. To understand this transformation, we analyzed the odor representation in large populations of individual M/T cells in the Xenopus OB. The spontaneous [Ca2+] activities of M/T cells appeared to be irregular, but there were groups of spatially distributed neurons showing synchronized [Ca2+] activities. These neurons were always connected to the same glomerulus. Odorants elicited complex spatiotemporal response patterns in M/T cells where nearby neurons generally showed little correlation. But the responses of neurons connected to the same glomerulus were virtually identical, irrespective of whether the responses were excitatory or inhibitory, and independent of the distance between them. Synchronous neurons received correlated EPSCs and were coupled by electrical conductances that could account for the correlated responses. Thus, at the output stage of the OB, odors are represented by modules of distributed and synchronous M/T cells associated with the same glomeruli. This allows for parallel input to higher brain centers.
Complete modification of TCR specificity and repertoire selection does not perturb a CD8+ T cell immunodominance hierarchy

Understanding T cell immunodominance hierarchies is fundamental to the development of cellular-based vaccines and immunotherapy. A combination of influenza virus infection in C57BL/6J mice and reverse genetics is used here to dissect the role of T cell antigen receptor (TCR) repertoire in the immunodominant DbNP366CD8+ T cell response. Infection with an engineered virus (NPM6A) containing a single alanine (A) mutation at the critical p6 NP366–374 residue induced a noncross-reactive CD8+ T cell response characterized by a novel, narrower TCR repertoire per individual mouse that was nonetheless equivalent in magnitude to that generated after WT virus challenge. Although of lower overall avidity, the levels of both cytotoxic T lymphocyte activity and cytokine production were comparable with those seen for the native response. Importantly, the overdominance profile characteristic of secondary DbNP366-specific clonal expansions was retained for the NPM6A mutant. The primary determinants of immunodominance in this endogenous, non-TCR-transgenic model of viral immunity are thus independent of TCR repertoire composition and diversity. These findings both highlight the importance of effective antigen dose for T cell vaccination and/or immunotherapy and demonstrate the feasibility of priming the memory T cell compartment with engineered viruses to protect against commonly selected mutants viral (or tumor) escape mutants.
Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer

Elevated MET receptor tyrosine kinase correlates with poor outcome in breast cancer, yet the reasons for this are poorly understood. We thus generated a transgenic mouse model targeting expression of an oncogenic Met receptor (Metmt) to the mammary epithelium. We show that Metmt induces mammary tumors with multiple phenotypes. These reflect tumor subtypes with gene expression and immunostaining profiles sharing similarities to human basal and luminal breast cancers. Within the basal subtype, Metmt induces tumors with signatures of WNT and epithelial to mesenchymal transition (EMT). Among human breast cancers, MET is primarily elevated in basal and ERBB2-positive subtypes with poor prognosis, and we show that MET, together with EMT marker, SNAIL, are highly predictive of poor prognosis in lymph node-negative patients. By generating a unique mouse model in which the Met receptor tyrosine kinase is expressed in the mammary epithelium, along with the examination of MET expression in human breast cancer, we have established a specific link between MET and basal breast cancer. This work identifies basal breast cancers and, additionally, poor-outcome breast cancers, as those that may benefit from anti-MET receptor therapies.
Expanding the repertoire of DNA shape features for genome-scale studies of transcription factor binding

Abstract Uncovering the mechanisms that affect the binding specificity of transcription factors (TFs) is critical for understanding the principles of gene regulation. Although sequence-based models have been used successfully to predict TF binding specificities, we found that including DNA shape information in these models improved their accuracy and interpretability. Previously, we developed a method for modeling DNA binding specificities based on DNA shape features extracted from Monte Carlo (MC) simulations. Prediction accuracies of our models, however, have not yet been compared to accuracies of models incorporating DNA shape information extracted from X-ray crystallography (XRC) data or Molecular Dynamics (MD) simulations. Here, we integrated DNA shape information extracted from MC or MD simulations and XRC data into predictive models of TF binding and compared their performance. Models that incorporated structural information consistently showed improved performance over sequence-based models regardless of data source. Furthermore, we derived and validated nine additional DNA shape features beyond our original set of four features. The expanded repertoire of 13 distinct DNA shape features, including six intra-base pair and six inter-base pair parameters and minor groove width, is available in our R/Bioconductor package DNAshapeR and enables a comprehensive structural description of the double helix on a genome-wide scale.
Transforming activity of AML1-ETO is independent of CBFβ and ETO interaction but requires formation of homo-oligomeric complexes

Although both heterodimeric subunits of core binding factors (AML1/RUNX1 and CBFβ) essential for normal hematopoiesis are frequently mutated to form different chimeric fusion proteins in acute leukemia, the underlying molecular mechanisms and structural domains required for cellular transformation remain largely unknown. Despite the critical role of CBFβ for wild-type AML1 function and its direct involvement in chromosomal translocation, we demonstrate that both the expression and interaction with CBFβ are superfluous for AML1-ETO (AE)-mediated transformation of primary hematopoietic cells. Similarly, the hetero-oligomeric interaction with transcriptional repressor ETO family proteins and the highly conserved NHR1 domain in AE fusion are also dispensable for transforming activity. In contrast, AE-mediated transformation is critically dependent on the DNA binding and homo-oligomeric properties of the fusion. Abolishment of homo-oligomerization by a small-molecule inhibitor could specifically suppress AML1 fusion-mediated transformation of primary hematopoietic cells. Together, these results not only identify the essential molecular components but also potential avenues for therapeutic targeting of AE-mediated leukemogenesis.
Group Interventions with Cancer Patients

Abstract Cancer support groups have become increasingly available to patients over the last two decades. Although the various patient groups differ in their philosophy, membership, and aims, the majority can be categorized as predominantly “supportive” or “psychoeduca-tional” in their approach. To date, there is little evidence regarding the relative benefits of the two types of group in improving patients' psychological outcomes. This article presents a critical review of the evidence for the relative efficacy of the two approaches. A search of the literature using CD-ROM databases identified 15 studies of acceptable design that quantitatively evaluated psychological outcomes of one or both types of group intervention. Although some findings have been inconsistent, the majority of evidence suggests that patients who attend psychoeducational groups experience greater benefits than do those who attend purely supportive groups. Further well-designed research in this area is needed to identify specific patient cohorts that are most likely to benefit from each approach.
Phosphorylation of p53 by IκB kinase 2 promotes its degradation by β-TrCP

Functional inactivation of p53 and constitutive activation of the NF-κB pathway has been associated with several human cancers. In this study, we show that IκB kinase 2 (IKK2/IKKβ), which is critical for NF-κB activation, also phosphorylates p53. Phosphorylation of p53 at serines 362 and 366 by IKK2 leads to its recruitment to and ubiquitination by β-TrCP1. Degradation of ubiquitinated p53 is independent of Mdm2, because it occurs in both wild-type and Mdm2−/− cells. SiRNA-mediated reduction in the levels of β-TrCP1 and other members of the SCFβ−TrCP1E3 ubiquitin ligase complex or overexpression of a dominant negative form of β-TrCP1 enhances p53 stability. Substitutions at Ser-362 and 366 of p53 by alanines (p53 AA) result in reduced phosphorylation of p53 by IKK2, decreased association with β-TrCP1, and thus increased stability of p53 and expression of p53 target genes such as p21, altering the G1 phase of the cell cycle. Our results identify IKK2 and β-TrCP1 as novel regulators of the p53 pathway and suggest that blocking of IKK2 and β-TrCP1 could be a means of regulating p53 stability and thereby modulating its biological activity.
CIB1 functions as a Ca2+-sensitive modulator of stress-induced signaling by targeting ASK1

Calcium and integrin binding protein 1 (CIB1) is a Ca2+-binding protein of 22 kDa that was initially identified as a protein that interacts with integrin αIIb. Although it interacts with various proteins and has been implicated in diverse cellular functions, the molecular mechanism by which CIB1 regulates intracellular signaling networks has remained unclear. We now show that, by targeting apoptosis signal-regulating kinase 1 (ASK1), CIB1 negatively regulates stress-activated MAPK signaling pathways. CIB1 was thus shown to bind to ASK1, to interfere with the recruitment of TRAF2 to ASK1, and to inhibit the autophosphorylation of ASK1 on threonine-838, thereby blocking ASK1 activation. Furthermore, CIB1 mitigated apoptotic cell death initiated either by TNF-α in breast cancer MCF7 cells or by 6-hydroxydopamine (6-OHDA) in dopaminergic cells. Ca2+ influx induced by membrane depolarization reversed the inhibitory effect of CIB1 on 6-OHDA-induced ASK1 activation and cell death in dopaminergic neurons. These observations thus suggest that CIB1 functions as a Ca2+-sensitive negative regulator of ASK1-mediated signaling events.
Elaborate Positioning of Nanowire Arrays Contributed by Highly Adhesive Superhydrophobic Pillar‐Structured Substrates

Elaborate positioning of nanowire arrays can be generated upon highly adhesive superhydrophobic pillar-structured silicon substrates. The site of each nanowire can be precisely positioned by well designed tip-structured micropillars, yielding on-demand nanowire patterns. This approach might affect existing applications and enable new opportunities in organically functional devices and bio/chemical sensors.
Quantum‐Dot‐Tagged Reduced Graphene Oxide Nanocomposites for Bright Fluorescence Bioimaging and Photothermal Therapy Monitored In Situ

Quantum-dot-tagged reduced graphene oxide (QD-rGO) nanocomposites (left) internalized into targeted tumor cells display bright fluorescence from the QDs (right); by absorbing NIR radiation incident on the rGO and converting it into heat, they also cause simultaneous cell death and fluorescence reduction (bottom). The nanocomposite is thus capable of tumor imaging, photothermal therapy and in situ monitoring of treatment in progress.
A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is usually described as a pathological proliferation of prostatic fibroblasts/myofibroblasts and epithelial cells. In the present study of BPH samples, we have made a morphological and immunohistochemical study of BPH prostatic sections using markers of proliferation, apoptosis, hormone receptors, and TGF-β signaling. We found no evidence of proliferation in the stroma but in the epithelium of some ducts; 0.7% of the basal and 0.4% of luminal cells were positive for Ki67 and PCNA. Androgen receptor and estrogen receptor beta (ERβ)1 and ERβcx were abundant in both stromal and epithelial compartments but cells expressing ERα were very rare. What was very common in all BPH samples was the following: (i) regions of the ductal epithelium where the epithelial cells did not express E-cadherin, had lost their polarization, and become spindle shaped (the nuclei of these cells were strongly positive for pSmad 3 and Snail); and (ii) regions where the walls of the blood vessels were extremely thick and there was loss of endothelial layer. Loss of E-cadherin, increased pSmad 3, and high expression of Snail are all characteristic of epithelial-mesenchymal transition (EMT). We conclude that BPH is not a disease of prostatic stromal proliferation but rather of accumulation of mesenchymal-like cells derived from the prostatic epithelium and the endothelium. TGF-β is thought to play a key role in EMT. Our data suggests that TGF-β/Smad should be considered as targets for treatment of BPH.