Global gene expression profiling in human lung cells exposed to cobalt.

International audienceBACKGROUND: It has been estimated that more than 1 million workers in the United States are exposed to cobalt. Occupational exposure to 59 Co occurs mainly via inhalation and leads to various lung diseases. Cobalt is classified by the IARC as a possible human carcinogen (group 2B). Although there is evidence for in vivo and in vitro toxicity, the mechanisms of cobalt-induced lung toxicity are not fully known. The purpose of this work was to identify potential signatures of acute cobalt exposure using a toxicogenomic approach. Data analysis focused on some cellular processes and protein targets that are thought to be relevant for carcinogenesis, transport and biomarker research. RESULTS: A time course transcriptome analysis was performed on A549 human pulmonary cells, leading to the identification of 85 genes which are repressed or induced in response to soluble 59 Co. A group of 29 of these genes, representing the main biological functions, was assessed by quantitative RT-PCR. The expression profiles of six of them were then tested by quantitative RT-PCR in a time-dependent manner and three modulations were confirmed by Western blotting. The 85 modulated genes include potential cobalt carriers (FBXL2, ZNT1, SLC12A5), tumor suppressors or transcription factors (MAZ, DLG1, MYC, AXL) and genes linked to the stress response (UBC, HSPCB, BNIP3L). We also identified nine genes coding for secreted proteins as candidates for biomarker research. Of those, TIMP2 was found to be down-regulated and this modulation was confirmed, in a dose-dependent manner, at protein level in the supernatant of exposed cells. CONCLUSION: Most of these genes have never been described as related to cobalt stress and provide original hypotheses for further study of the effects of this metal ion on human lung epithelial cells. A putative biomarker of cobalt toxicity was identified

Dissecting the neuronal basis of threat responding in mice

Environmental threats demand adaptive defensive responses of an organism that ensure its survival. Extreme stressors, however, can unbalance stress homeostasis and lead to long-term changes that impair appropriate defensive behaviors and emotional responses. In my thesis, I assessed (1) the interaction of two stress-related neuromodulatory systems, (2) the effects of a traumatic incident on brain volume and hyperarousal, and (3) sonic vocalization as a defensive behavior in mice, and discussed the topics in three independent studies.In the first study, I evaluated the interaction of two regulatory systems with respect to fear, anxiety, and trauma-related behaviors. Although the endocannabinoid and the corticotropin-releasing factor (CRF) systems are well described in modulating stressrelatedresponses, the direct interaction of both systems remained poorly understood. The generation of a new conditional knockout mouse line that selectively lacked the expression of the cannabinoid type 1 (CB1) receptor in CRF-positive neurons presented no differences in various tests of fear and anxiety-related behaviors under basal conditions or after a traumatic event. Also stress hormone levels were unaffected. However, male knockout animals exhibited a significantly increased acoustic startle response thus suggesting a specific involvement of CB1-CRF interactions in controlling arousal.In the second study, I assessed the consequences of a traumatic experience on behavior and grey matter volume in mice. Whole-brain deformation-based morphometry (DBM) by means of magnetic resonance imaging (MRI) after incubation of a traumatic incident showed changes in the dorsal hippocampus and the reticular nucleus. Using the severity of hyperarousal as regressor for cross-sectional volumetric differences between traumatized mice and controls revealed a negative correlation with the dorsal hippocampus. Further, longitudinal analysis including volumetric measurements before and after the traumatic incident showed that volume reductions in the globus pallidus reflect trauma-related changes in hyperarousal severity.In the third study, I characterized sonic vocalization as a defensive behavior in mice. Mice bred for high anxiety-related behavior (HAB) were found to have a high disposition to emit audible squeaks when taken by the tail which was not the case for any of the other five mouse lines tested. The calls emitted had a fundamental frequency of 3.8 kHz and were shown to be sensitive to anxiolytic but not panicolytic compounds. Manganese-enhanced MRI (MEMRI) scans pointed towards an increased tonic activity, among others, in the periaqueductal grey (PAG). Inhibition of the dorsal PAG by muscimol not only completely abolished sonic vocalization, but also reduced anxiety-like behavior. This suggests that sonic vocalization of mice is related to anxiety and controlled by the PAG. To explore the ecological relevance of defensive vocalization, I performed playback experiments with conspecifics and putative predators. Squeaks turned out to be aversive to HAB mice but became appetitive to both mice and rats when a stimulus mouse was present during playback.Collectively, the results of this thesis provide novel insights into fear and anxiety-related behaviors and shine light onto their mechanistic basis and ecological relevance

Permasalahan Pembinaan Warga Gereja Di Kewari

Ruat Diana, This article discusses the issue of church community development in Kewari. The main focus of this article is the difficulty of fostering church members to the Kewari community. Through this research, the authors describe the factors behind the difficulty of fostering church members in Kewari. These factors are seen from social and historical aspects. The author assesses the importance of exposing it as a reflection in carrying out church community development. The pattern of community life, language differences and the slow adjustment of language, the level of community education, and the beliefs of the community became a factor of difficulty of building church people in Kewari Ruat Diana, Permasalahan Pembinaan Warga Gereja di Kewari. Artikel ini membahas ten-tang permasalahan pembinaan warga gereja di Kewari. Fokus utama dari artikel ini adalah faktor kesulit-an pembinaan warga gereja kepada masyarakat Kewari. Melalui penelitian ini, penulis menggambarkan faktor-faktor yang melatarbelakangi kesulitan pembinaan warga gereja di Kewari. Faktor-faktor tersebut dilihat dari aspek sosial dan sejarah. Penulis menilai pentingnya memaparkan hal tersebut sebagai sebuah refleksi dalam melaksanakan pembinaan warga gereja. Pola hidup masyarakat, perbedaan bahasa dan lambatnya penyesuaian bahasa, tingkat pendidikan masyarakat, dan keyakinan masyarakat menjadi faktor kesulitan pembinaan warga gereja di Kewari

A method for high-energy, low-dose mammography using edge illumination x-ray phase-contrast imaging

Since the breast is one of the most radiosensitive organs, mammography is arguably the area where lowering radiation dose is of the uttermost importance. Phase-based x-ray imaging methods can provide opportunities in this sense, since they do not require x-rays to be stopped in tissue for image contrast to be generated. Therefore, x-ray energy can be considerably increased compared to those usually exploited by conventional mammography. In this article we show how a novel, optimized approach can lead to considerable dose reductions. This was achieved by matching the edge-illumination phase method, which reaches very high angular sensitivity also at high x-ray energies, to an appropriate image processing algorithm and to a virtually noise-free detection technology capable of reaching almost 100% efficiency at the same energies. Importantly, while proof-of-concept was obtained at a synchrotron, the method has potential for a translation to conventional sources

Tinjauan Psiko-Teologi Terhadap Fenomena Kekerasan Dalam Pacaran Pada Remaja

Fenomena kekerasan dalam berpacaran bukan hanya terjadi di ruang tertutup atau pribadi saja melainkan sangat mudah ditemukan di ruang publik seperti halaman sekolah, tempat rental komputer, taman, trotoar, kendaraan umum, pada penumpang kendaraan roda dua di tengah lalu lintas. Dan ketika peristiwa itu berlangsung serta disaksikan oleh masyarakat umum, pelaku dan korban tidak merasa terganggu, rikuh, malu, atau berhenti. Padahal kekerasan dalam pacaran di kalangan remaja merupakan salah satu akses kepada kekerasan dalam rumah tangga, apabila hal ini tidak ditangani secara benar sebelum berkelanjutan dengan korban yang mengalami dampak pada fisik, psikis, sosial, moral, ekonomi dan masa depan generasi penerus. Metode yang digunakan adalah penelitian deskriptif dengan mengkaji fenomena kekerasan dalam pacaran dari sudut pandang Alkitab dan psikologi, dimana secara psikologis kekerasan seksual yang terjadi pada masa remaja berdampak negatif bagi pelaku maupun korban kekerasan seksual. Adapun kekerasan pada masa berpacaran dapat disebabkan karena remaja mengalami loncatan akibat gejolak hormon dan pesatnya teknologi informasi. Secara teologis hubungan seks sebelum menikah adalah tindakan merusak kehidupan para pelakunya dan kekerasan pada masa berpacaran merupakan tindakan yang bertentangan dengan konsep imago dei.  The phenomenon of dating violence does not only occur in closed or private spaces but is very easy to find in public spaces such as school yards, computer rental places, parks, sidewalks, public transportation, on two-wheeled vehicle passengers in the middle of traffic. And when the event took place and was witnessed by the general public, the perpetrators and victims did not feel disturbed, uncomfortable, embarrassed, or stopped. Whereas violence in courtship among adolescents is one access to domestic violence, if this is not handled properly before it is sustained with victims who have an impact on the physical, psychological, social, moral, economic and future generations. The method used is descriptive research by examining the phenomenon of dating violence from the perspective of the Bible and psychology, where psychologically sexual violence that occurs during adolescence has a negative impact on perpetrators and victims of sexual violence. The violence during dating can be caused by adolescents experiencing jumps due to hormone fluctuations and rapid information technology. Theologically sex before marriage is an act of destroying the lives of the perpetrators and violence during dating is an action that is contrary to the concept of Imago dei.Â

Radiation hardness studies of a 130 nm Silicon Germanium BiCMOS technology with a dedicated ASIC

We present the radiation hardness studies on the bipolar devices of the 130 nm 8WL Silicon Germanium (SiGe) BiCMOS technology from IBM. This technology has been proposed as one of the candidates for the Front-End (FE) readout chip of the upgraded Inner Detector (ID) and the Liquid Argon Calorimeter (LAr) of the ATLAS Upgrade experiment. After neutron irradiations, devices remain at acceptable performances at the maximum radiation levels expected in the Si tracker and LAr calorimeter

Makna Penebusan Dalam Upacara Tiwah Sebagai Pendekatan Kontekstualisasi Injil

Budaya dalam agama Hindu Kaharingan, yaitu budaya Tiwah merupakan sebuah bentuk budaya yang dengan pelaksanaan upacara yang unik. Dalam proses pelaksaannya, upacara tiwah mengandung prosesi yang beragam dan penuh makna. Melalui makna upacara tiwah ini, penulis mengadopsikannya sebagai kontekstualisasi media untuk menyampaikan Injil. Penulis memahami pemahaman makna dan selanjutnya Kristus dalam upacara tiwah yang dilakukan oleh umat Hindu Kaharingan. Dengan menggunakan pendekatan kualitatif dan penelusuran pelaksanaan upacara Tiwah melalui wawancara dan literatur yang ada, penulis mengkaji makna dalam upacara Tiwah tersebut yang kemudian disaring dengan metode yang mengubah, dan membuah dan firman Tuhan sebagai tolak ukurnya. Yesus sebagai korban dalam upacara tiwah, Yesus sebagai jalan menuju “Lewu Tatau” , dan Yesus sebagai pengantara antara manusia dan “Ranying Hatalla”. Poin-poin tersebut menjadi hasil pembahasan dalam pendekatan kontekstualisasi Injil dalam upacara Tiwah