Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and non-radioactive in situ hybridization techniques: diagnosis of trisomy 18 with probe L1.84

The localization of chromosome 18 in human interphase nuclei is demonstrated by use of radioactive and nonradioactive in situ hybridization techniques with a DNA clone designated L1.84. This clone represents a distinct subpopulation of the repetitive human alphoid DNA family, located in the centric region of chromosome 18. Under stringent hybridization conditions hybridization of L1.84 is restricted to chromosome 18 and reflects the number of these chromosomes present in the nuclei, namely, two in normal diploid human cells and three in nuclei from cells with trisomy 18. Under conditions of low stringency, cross-hybridization with other subpopulations of the alphoid DNA family occurs in the centromeric regions of the whole chromosome complement, and numerous hybridization sites are detected over interphase nuclei. Detection of chromosome-specific target DNAs by non-radioactive in situ hybridization with appropriate DNA probes cloned from individual chromosomal subregions presents a rapid means of identifying directly numerical or even structural chromosome aberrations in the interphase nucleus. Present limitations and future applications of interphase cytogenetics are discussed

Broadened Population-Level Frequency Tuning in Human Auditory Cortex of Portable Music Player Users

Nowadays, many people use portable players to enrich their daily life with enjoyable music. However, in noisy environments, the player volume is often set to extremely high levels in order to drown out the intense ambient noise and satisfy the appetite for music. Extensive and inappropriate usage of portable music players might cause subtle damages in the auditory system, which are not behaviorally detectable in an early stage of the hearing impairment progress. Here, by means of magnetoencephalography, we objectively examined detrimental effects of portable music player misusage on the population-level frequency tuning in the human auditory cortex. We compared two groups of young people: one group had listened to music with portable music players intensively for a long period of time, while the other group had not. Both groups performed equally and normally in standard audiological examinations (pure tone audiogram, speech test, and hearing-in-noise test). However, the objective magnetoencephalographic data demonstrated that the population-level frequency tuning in the auditory cortex of the portable music player users was significantly broadened compared to the non-users, when attention was distracted from the auditory modality; this group difference vanished when attention was directed to the auditory modality. Our conclusion is that extensive and inadequate usage of portable music players could cause subtle damages, which standard behavioral audiometric measures fail to detect in an early stage. However, these damages could lead to future irreversible hearing disorders, which would have a huge negative impact on the quality of life of those affected, and the society as a whole

Polar vortex formation in giant-planet atmospheres due to moist convection

A strong cyclonic vortex has been observed on each of Saturn’s poles, coincident with a local maximum in observed tropospheric temperature. Neptune also exhibits a relatively warm, although much more transient, region on its south pole. Whether similar features exist on Jupiter will be resolved by the 2016 Juno mission. Energetic, small-scale storm-like features that originate from the water-cloud level or lower have been observed on each of the giant planets and attributed to moist convection, suggesting that these storms play a significant role in global heat transfer from the hot interior to space. Nevertheless, the creation and maintenance of Saturn’s polar vortices, and their presence or absence on the other giant planets, are not understood. Here we use simulations with a shallow-water model to show that storm generation, driven by moist convection, can create a strong polar cyclone throughout the depth of a planet’s troposphere. We find that the type of shallow polar flow that occurs on a giant planet can be described by the size ratio of small eddies to the planetary radius and the energy density of its atmosphere due to latent heating from moist convection. We suggest that the observed difference in these parameters between Saturn and Jupiter may preclude a Jovian polar cyclone.National Science Foundation (U.S.). Graduate Research FellowshipNational Science Foundation (U.S.) (ATM-0850639)National Science Foundation (U.S.) (AGS-1032244)National Science Foundation (U.S.) (AGS-1136480)United States. Office of Naval Research (N00014-14-1-0062

Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential

Background: The metastatic disease rather than the primary tumor itself is responsible for death in most solid tumors, including breast cancer. The role of matrix metalloproteinases ( MMPs), tissue inhibitors of MMPs (TIMPs) and Reversion-inducing cysteine-rich protein with Kazal motifs ( RECK) in the metastatic process has previously been established. However, in all published studies only a limited number of MMPs/MMP inhibitors was analyzed in a limited number of cell lines. Here, we propose a more comprehensive approach by analyzing the expression levels of several MMPs (MMP-2, MMP-9 and MMP-14) and MMP inhibitors (TIMP-1, TIMP-2 and RECK) in different models ( five human breast cancer cell lines, 72 primary breast tumors and 30 adjacent normal tissues). Methods: We analyzed the expression levels of MMP-2, MMP-9 and MMP-14 and their inhibitors (TIMP-1, TIMP-2 and RECK) by quantitative RT-PCR (qRT-PCR) in five human breast cancer cell lines presenting increased invasiveness and metastatic potential, 72 primary breast tumors and 30 adjacent normal tissues. Moreover, the role of cell-extracellular matrix elements interactions in the regulation of expression and activity of MMPs and their inhibitors was analyzed by culturing these cell lines on plastic or on artificial ECM (Matrigel). Results: The results demonstrated that MMPs mRNA expression levels displayed a positive and statistically significant correlation with the transcriptional expression levels of their inhibitors both in the cell line models and in the tumor tissue samples. Furthermore, the expression of all MMP inhibitors was modulated by cell-Matrigel contact only in highly invasive and metastatic cell lines. The enzyme/inhibitor balance at the transcriptional level significantly favors the enzyme which is more evident in tumor than in adjacent non-tumor tissue samples. Conclusion: Our results suggest that the expression of MMPs and their inhibitors, at least at the transcriptional level, might be regulated by common factors and signaling pathways. Therefore, the multi-factorial analysis of these molecules could provide new and independent prognostic information contributing to the determination of more adequate therapy strategies for each patient.`Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Pesquisa (CNPq)Financiadora de Estudos e Projetos (FINEP)Pro-Reitoria da Universidade de Sao Paulo (PRP-USP

Retuning of Inferior Colliculus Neurons Following Spiral Ganglion Lesions: A Single-Neuron Model of Converging Inputs

Lesions of spiral ganglion cells, representing a restricted sector of the auditory nerve array, produce immediate changes in the frequency tuning of inferior colliculus (IC) neurons. There is a loss of excitation at the lesion frequencies, yet responses to adjacent frequencies remain intact and new regions of activity appear. This leads to immediate changes in tuning and in tonotopic progression. Similar effects are seen after different methods of peripheral damage and in auditory neurons in other nuclei. The mechanisms that underlie these postlesion changes are unknown, but the acute effects seen in IC strongly suggest the “unmasking” of latent inputs by the removal of inhibition. In this study, we explore computational models of single neurons with a convergence of excitatory and inhibitory inputs from a range of characteristic frequencies (CFs), which can simulate the narrow prelesion tuning of IC neurons, and account for the changes in CF tuning after a lesion. The models can reproduce the data if inputs are aligned relative to one another in a precise order along the dendrites of model IC neurons. Frequency tuning in these neurons approximates that seen physiologically. Removal of inputs representing a narrow range of frequencies leads to unmasking of previously subthreshold excitatory inputs, which causes changes in CF. Conversely, if all of the inputs converge at the same point on the cell body, receptive fields are broad and unmasking rarely results in CF changes. However, if the inhibition is tonic with no stimulus-driven component, then unmasking can still produce changes in CF

Effects of Heavy Metals and Arbuscular Mycorrhiza on the Leaf Proteome of a Selected Poplar Clone: A Time Course Analysis

Arbuscular mycorrhizal (AM) fungi establish a mutualistic symbiosis with the roots of most plant species. While receiving photosynthates, they improve the mineral nutrition of the plant and can also increase its tolerance towards some pollutants, like heavy metals. Although the fungal symbionts exclusively colonize the plant roots, some plant responses can be systemic. Therefore, in this work a clone of Populus alba L., previously selected for its tolerance to copper and zinc, was used to investigate the effects of the symbiosis with the AM fungus Glomus intraradices on the leaf protein expression. Poplar leaf samples were collected from plants maintained in a glasshouse on polluted (copper and zinc contaminated) or unpolluted soil, after four, six and sixteen months of growth. For each harvest, about 450 proteins were reproducibly separated on 2DE maps. At the first harvest the most relevant effect on protein modulation was exerted by the AM fungi, at the second one by the metals, and at the last one by both treatments. This work demonstrates how importantly the time of sampling affects the proteome responses in perennial plants. In addition, it underlines the ability of a proteomic approach, targeted on protein identification, to depict changes in a specific pattern of protein expression, while being still far from elucidating the biological function of each protein

The “conscious pilot”—dendritic synchrony moves through the brain to mediate consciousness

Cognitive brain functions including sensory processing and control of behavior are understood as “neurocomputation” in axonal–dendritic synaptic networks of “integrate-and-fire” neurons. Cognitive neurocomputation with consciousness is accompanied by 30- to 90-Hz gamma synchrony electroencephalography (EEG), and non-conscious neurocomputation is not. Gamma synchrony EEG derives largely from neuronal groups linked by dendritic–dendritic gap junctions, forming transient syncytia (“dendritic webs”) in input/integration layers oriented sideways to axonal–dendritic neurocomputational flow. As gap junctions open and close, a gamma-synchronized dendritic web can rapidly change topology and move through the brain as a spatiotemporal envelope performing collective integration and volitional choices correlating with consciousness. The “conscious pilot” is a metaphorical description for a mobile gamma-synchronized dendritic web as vehicle for a conscious agent/pilot which experiences and assumes control of otherwise non-conscious auto-pilot neurocomputation

Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology DepartmentUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology and Pathology DepartmentsUNIFESP, EPM, Dermatology DepartmentUNIFESP, EPM, Dermatology and Pathology DepartmentsSciEL

Synthesis of 2-azidoethyl α-d-mannopyranoside orthogonally protected and selective deprotections

4 páginas, 1 figura, 2 esquemas.We present the synthesis of a fully orthogonally protected mannosyl glycoside 1 and the corresponding methods for selective deprotections. Mannosyl glycoside 1 contains a functionalized linker at the anomeric position to allow for the attachment of carbohydrate units to scaffolds in order to prepare carbohydrate multivalent systems.We would like to thank FIS (PI030093), for financial supportPeer reviewe