Twofold topological phase transitions induced by third-nearest-neighbor interactions in 1D chains

Strong long-range interactions up to third nearest neighbors may induce a topological phase transition in one-dimensional chains. Unlike the Su-Schrieffer-Heeger model, this transition from trivial to topological phase occurs with the emergence of a pseudospin valley structure and a twofold nontrivial topological phase. Within a tight-binding approach, these topological phases are analyzed in detail and it is shown that the low-energy excitations follow a modified Dirac equation. An experimental realization in a one-dimensional elastic chain, where it is feasible to tune directly the third-nearest-neighbor interaction strength, is proposed.Comment: 6 pages, 3 figure

Gambogic Acid, a Natural Product Inhibitor of Hsp90

A high-throughput screening of natural product libraries identified (−)-gambogic acid (1), a component of the exudate of Garcinia harburyi, as a potential Hsp90 inhibitor, in addition to the known Hsp90 inhibitor celastrol (2). Subsequent testing established that 1 inhibited cell proliferation, brought about the degradation of Hsp90 client proteins in cultured cells, and induced the expression of Hsp70 and Hsp90, which are hallmarks of Hsp90 inhibition. Gambogic acid also disrupted the interaction of Hsp90, Hsp70, and Cdc37 with the heme-regulated eIF2α kinase (HRI, an Hsp90-dependent client) and blocked the maturation of HRI in vitro. Surface plasmon resonance spectroscopy indicated that 1 bound to the N-terminal domain of Hsp90 with a low micromolar Kd, in a manner that was not competitive with the Hsp90 inhibitor geldanamycin (3). Molecular docking experiments supported the posit that 1 binds Hsp90 at a site distinct from Hsp90s ATP binding pocket. The data obtained have firmly established 1 as a novel Hsp90 inhibitor and have provided evidence of a new site that can be targeted for the development of improved Hsp90 inhibitors

The neurochemical basis of human cortical auditory processing: combining proton magnetic resonance spectroscopy and magnetoencephalography

BACKGROUND: A combination of magnetoencephalography and proton magnetic resonance spectroscopy was used to correlate the electrophysiology of rapid auditory processing and the neurochemistry of the auditory cortex in 15 healthy adults. To assess rapid auditory processing in the left auditory cortex, the amplitude and decrement of the N1m peak, the major component of the late auditory evoked response, were measured during rapidly successive presentation of acoustic stimuli. We tested the hypothesis that: (i) the amplitude of the N1m response and (ii) its decrement during rapid stimulation are associated with the cortical neurochemistry as determined by proton magnetic resonance spectroscopy. RESULTS: Our results demonstrated a significant association between the concentrations of N-acetylaspartate, a marker of neuronal integrity, and the amplitudes of individual N1m responses. In addition, the concentrations of choline-containing compounds, representing the functional integrity of membranes, were significantly associated with N1m amplitudes. No significant association was found between the concentrations of the glutamate/glutamine pool and the amplitudes of the first N1m. No significant associations were seen between the decrement of the N1m (the relative amplitude of the second N1m peak) and the concentrations of N-acetylaspartate, choline-containing compounds, or the glutamate/glutamine pool. However, there was a trend for higher glutamate/glutamine concentrations in individuals with higher relative N1m amplitude. CONCLUSION: These results suggest that neuronal and membrane functions are important for rapid auditory processing. This investigation provides a first link between the electrophysiology, as recorded by magnetoencephalography, and the neurochemistry, as assessed by proton magnetic resonance spectroscopy, of the auditory cortex

Ubiquitous Crossmodal Stochastic Resonance in Humans: Auditory Noise Facilitates Tactile, Visual and Proprioceptive Sensations

BACKGROUND: Stochastic resonance is a nonlinear phenomenon whereby the addition of noise can improve the detection of weak stimuli. An optimal amount of added noise results in the maximum enhancement, whereas further increases in noise intensity only degrade detection or information content. The phenomenon does not occur in linear systems, where the addition of noise to either the system or the stimulus only degrades the signal quality. Stochastic Resonance (SR) has been extensively studied in different physical systems. It has been extended to human sensory systems where it can be classified as unimodal, central, behavioral and recently crossmodal. However what has not been explored is the extension of this crossmodal SR in humans. For instance, if under the same auditory noise conditions the crossmodal SR persists among different sensory systems. METHODOLOGY/PRINCIPAL FINDINGS: Using physiological and psychophysical techniques we demonstrate that the same auditory noise can enhance the sensitivity of tactile, visual and propioceptive system responses to weak signals. Specifically, we show that the effective auditory noise significantly increased tactile sensations of the finger, decreased luminance and contrast visual thresholds and significantly changed EMG recordings of the leg muscles during posture maintenance. CONCLUSIONS/SIGNIFICANCE: We conclude that crossmodal SR is a ubiquitous phenomenon in humans that can be interpreted within an energy and frequency model of multisensory neurons spontaneous activity. Initially the energy and frequency content of the multisensory neurons' activity (supplied by the weak signals) is not enough to be detected but when the auditory noise enters the brain, it generates a general activation among multisensory neurons of different regions, modifying their original activity. The result is an integrated activation that promotes sensitivity transitions and the signals are then perceived. A physiologically plausible model for crossmodal stochastic resonance is presented

14-3-3epsilon contributes to tumour suppression in laryngeal carcinoma by affecting apoptosis and invasion

<p>Abstract</p> <p>Background</p> <p>14-3-3epsilon regulates a wide range of biological processes, including cell cycle control, proliferation, and apoptosis, and plays a significant role in neurogenesis and the formation of malignant tumours. However, the exact function and regulatory mechanism of 14-3-3epsilon in carcinogenesis have not been elucidated.</p> <p>Methods</p> <p>The expression of <it>14-3-3epsilon </it>was assessed by RT-PCR and western blotting. The invasiveness and viability of Hep-2 cells were determined by the transwell migration assay and MTT assay, respectively. Cell cycle and apoptosis of Hep-2 cells were detected by flow cytometry.</p> <p>Results</p> <p>The mRNA and protein expression of <it>14-3-3epsilon </it>in larynx squamous cell carcinoma (LSCC) tissues were significantly lower than those in clear surgical margin tissues. Statistical analysis showed that the 14-3-3epsilon protein level in metastatic lymph nodes was lower than that in paired tumour tissues. In addition, the protein level of 14-3-3epsilon in stage III or IV tumours was significantly lower than that in stage I or II tumours. Compared with control Hep-2 cells, the percentages of viable cells in the 14-3-3epsilon-GFP and negative control GFP groups were 36.68 ± 14.09% and 71.68 ± 12.10%, respectively. The proportions of S phase were 22.47 ± 3.36%, 28.17 ± 3.97% and 46.15 ± 6.82%, and the apoptotic sub-G1 populations were 1.23 ± 1.02%, 2.92 ± 1.59% and 13.72 ± 3.89% in the control, negative control GFP and 14-3-3epsilon-GFP groups, respectively. The percentages of the apoptotic cells were 0.84 ± 0.25%, 1.08 ± 0.24% and 2.93 ± 0.13% in the control, negative control GFP and 14-3-3epsilon-GFP groups, respectively. The numbers of cells that penetrated the filter membrane in the control, negative control GFP and 14-3-3epsilon-GFP groups were 20.65 ± 1.94, 17.63 ± 1.04 and 9.1 ± 0.24, respectively, indicating significant differences among the different groups.</p> <p>Conclusions</p> <p>Decreased expression of <it>14-3-3epsilon </it>in LSCC tissues contributes to the initiation and progression of LSCC. <it>14-3-3epsilon </it>can promote apoptosis and inhibit the invasiveness of LSCC.</p

Impacto de un programa intervención em alunos del segundo ciclo

O objetivo do presente estudo consistiuem avaliar um programa de intervenção junto a alunos do 2º ciclo de escolaridade nas seguintes dimensões: tomada de decisão, conhecimentos sobre sexualidade, competências sociais, assertividade e autoconceito. Metodologia: Participaram 145 alunos, distribuídos pelos grupos controle e experimental. Os instrumentos utilizados foram: TCU Decision-Making; Questionário de Conhecimentos sobre Sexualidade; Assertion Self-Statement Test- Revised; Questionário de Competências Sociais; Piers-Harris Children’s Self-Concept Scale. Os resultados revelaram diferenças no pós-teste entre os grupos ao nível da sexualidade. Verificaram-se diferenças do pré-teste para o pós-teste no grupo experimental nos níveis da sexualidade, da assertividade e das competências sociais. No grupo experimental encontraram-se associações positivas entre tomada de decisão, competências sociais e assertividade, bem como entre sexualidade, competências sociais e autoconceito, no pós-teste. Os preditores da assertividade no pós-teste foram tomada de decisão, sexualidade e competências sociais. Como conclusão, os resultados enfatizam a importância de intervenção junto a adolescentes, particularmente na tomada de decisão, na sexualidade e nas competências sociais. Palavras-chave: Habilidades sociais, sexualidade, autoconceito.In this study we evaluate an intervention program in the following dimensions: Decision Making, Knowledge on Sexuality, Social Skills, Assertiveness and Self-Concept with students in 5th and 6th grade. Methodology: 145 students participated in the study divided by control and experimental group. The instruments used were: Decision-Making TCU, Knowledge on Sexuality Questionnaire; Assertion Self-Statement Test-Revised;Social Skills Questionnaire, and Piers-Harris Children's Self- Concept Scale. The results indicate differences at post-test between the groups on knowledge regarding sexuality. There were also differences from pre-test to post-test in the experimental group on knowledge on sexuality, assertiveness and social skills. Positive associations among decision making, social skills and assertiveness were found as well as among knowledge on sexuality, social skills and self-concept, in the experimental group, in the pos-test. Finally, the predictors of assertiveness regarding health behaviors, in the pos-test were: decision making, knowledge regarding sexuality and social skills. The results emphasize the importance of intervention for adolescents in terms of health promotion particularly in decision making, sexuality and social skills.El objetivo del presente estudio fue evaluar un programa de intervención con alumnos del 2º ciclo de escolaridad en las siguientes dimensiones: Toma de Decisión, Conocimientos sobre Sexualidad, Habilidades Sociales, Asertividad y Autoconcepto. Metodología: Participaron 145 alumnos, distribuidos en grupo control y experimental. Los instrumentos utilizados fueron: TCU Decision-Making; Cuestionario de Conocimientos sobre Sexualidad; AssertionSelf-Statement Test-Revised; Cuestionario de Habilidades Sociais; Piers-Harris Children'sSelf-Concept Scale. Los resultados mostraron diferencias en el post-test entre los grupos en cuanto a la sexualidad. Se verificaron diferencias del pre-test para el post-teste en el grupo experimental, cuanto a sexualidad, asertividad y habilidades sociales. Se encontraron asociaciones positivas entre toma de decisión, habilidades sociales y asertividad, así como entre sexualidad,habilidades sociales yautoconcepto, en el post-test en el grupo experimental. Los predictores de la asertividad en el post-test fueron toma de decisión, sexualidad y habilidades sociales. Los resultados destacan la importancia de la intervención con adolescentes particularmente en la toma de decisiones, sexualidad y habilidades sociales.(undefined

Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry, constituting a new GWAS, a meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including ten new associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n = 16) of transcription factors among SLE susceptibility genes. This finding supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE