106 research outputs found

    Control of somatosensory cortical processing by thalamic posterior medial nucleus: A new role of thalamus in cortical function

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    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane- anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas.This work was supported by a grant from Ministerio de Economia y Competitividad (BFU2012- 36107

    Tumor Suppressor Pdcd4 Attenuates Sin1 Translation to Inhibit Invasion in Colon Carcinoma

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    Programmed cell death 4 (Pdcd4), a tumor invasion suppressor, is frequently downregulated in colorectal cancer and other cancers. In this study, we find that loss of Pdcd4 increases the activity of mammalian target of rapamycin complex 2 (mTORC2) and thereby upregulates Snail expression. Examining the components of mTORC2 showed that Pdcd4 knockdown increased the protein but not mRNA level of stress-activated-protein kinase interacting protein 1 (Sin1), which resulted from enhanced Sin1 translation. To understand how Pdcd4 regulates Sin1 translation, the SIN1 5′ untranslated region (5′UTR) was fused with luciferase reporter and named as 5′Sin1-Luc. Pdcd4 knockdown/knockout significantly increased the translation of 5′Sin1-Luc but not the control luciferase without the SIN1 5′UTR, suggesting that Sin1 5′UTR is necessary for Pdcd4 to inhibit Sin1 translation. Ectopic expression of wild-type Pdcd4 and Pdcd4(157–469), a deletion mutant that binds to translation initiation factor 4A (eIF4A), sufficiently inhibited Sin1 translation, and thus suppressed mTORC2 kinase activity and invasion in colon tumor cells. By contrast, Pdcd4(157–469)(D253A,D418A), a mutant that does not bind to eIF4A, failed to inhibit Sin1 translation, and consequently failed to repress mTORC2 activity and invasion. In addition, directly inhibiting eIF4A with silvestrol significantly suppressed Sin1 translation and attenuated invasion. These results indicate that Pdcd4-inhibited Sin1 translation is through suppressing eIF4A, and functionally important for suppression of mTORC2 activity and invasion. Moreover, in colorectal cancer tissues, the Sin1 protein but not mRNA was significantly upregulated while Pdcd4 protein was downregulated, suggesting that loss of Pdcd4 might correlate with Sin1 protein level but not mRNA level in colorectal cancer patients. Taken together, our work reveals a novel mechanism by which Pdcd4 inhibits Sin1 translation to attenuatemTORC2 activity and thereby suppresses invasion

    Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences and Countermeasures.

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    Circadian (∼ 24 hour) timing systems pervade all kingdoms of life, and temporally optimize behaviour and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behaviour and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these too are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally-driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioural and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important

    Topical antibiotics as a major contextual hazard toward bacteremia within selective digestive decontamination studies: a meta-analysis

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    PENGENDALIAN ORIENTASI WEBCAM SEBAGAI PENGAWAS RUANGAN DENGAN METODE KONTROL FUZZY

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    Suatu sistem keamanan yang baik sangat diperlukan untuk membantu mengurangi, mencegah dan mengatasi permasalahan kriminalitas yang terus meningkat. Saat ini kamera video telah diterapkan untuk mendukung sistem keamanan. Kamera akan merekam gambar atau obyek didepannya serta menyimpannya dalam media penyimpan yang dimiliki. Sistem keamanan yang diterapkan pada area yang luas akan membutuhkan perangkat monitoring dalam jumlah besar. Dengan menggunakan perangkat monitoring yang dapat bergerak bebas untuk memantau suatu ruangan, maka jumlah perangkat yang banyak dapat dikurangi, terlebih kalau perangkat tersebut dapat bergerak secara otomatis sehingga tidak diperlukan operator untuk menggerakkan perangkat monitoring tersebut. Dalam tugas akhir ini akan dirancang sistem pengendalian orientasi webcam yang difungsikan sebagai alat monitoring ruangan yang mampu mengikuti suatu obyek yang bergerak didepannya serta memposisikan obyek tersebut ditengah-tengah perekaman gambar sehingga dihasilkan mutu perekaman gambar yang bagus. Metode kontrol yang dipakai dalam pengendalian webcam adalah Fuzzy Logic Controller. Sedangkan bahasa pemrograman yang digunakan adalah Microsoft Visual Basic pada PC dan bahasa C embedded dalam mikrokontroler ATMEGA8535. Dari hasil pengujian didapatkan bahwa Pengendalian orientasi kamera mempunyai respon yang cukup baik terutama pada obyek diam yaitu dengan error steady state rata-rata ± 30 pixel. Error steady state terjadi karena karakteristik motor yang mempunyai dead zone yang cukup lebar. Motor bisa berputar jika diberikan minimal ±33% dutycycle PWM. Jika dalam area monitoring tidak terdapat obyek maka sistem akan melakukan scanning sampai ditemukan obyek. Pada pengawasan obyek bergerak, kamera akan melakukan pergerakan sama dengan arah pergerakan obyek baik untuk obyek berkecepatan lambat maupun cepat. Kecepatan maksimum webcam adalah ± 0,8 RPM. Prinsip dan respon pada obyek mejemuk hampir sama dengan obyek tunggal. Kata kunci : Pengendalian webcam, Fuzzy Logic Controller, mikrokontroler ATMEGA8535

    Enhancing the Interface for Ontology-Supported Homonym Search

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