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Reassurance-seeking in Internet: A prospective study of path to depression and Internet addiction
No full text目的：在網路成癮之研究領域中，憂鬱為最常被報告的共病問題，然而過去研究多為橫斷性研究，而未能釐清兩者的病理前後關係。因此，本研究欲以相隔四週之前瞻性研究設計，檢驗憂鬱先於網路成癮之病理路徑的可能性。考量現今網路人際溝通隨科技進展而越趨重要，本研究將以人際取向探討之。基於Coyne（1976b）憂鬱人際模式之論述，Joiner、Alfano及Metalsky（1992）認為尋求再保證乃惡化憂鬱之關鍵人際行為，本研究則進一步檢驗尋求再保證風格能否作為憂鬱與網路成癮之共同危險因子，並檢驗個體是否透過了現實/網路尋求再保證後果，而惡化了後續憂鬱與網路成癮。方法：研究參與者為網路招募之成年人，有效樣本共181名（43.1%男性，56.9%女性，年齡範圍為20至39歲）。參與者以匿名方式作答，於初始時間點填答貝氏憂鬱量表第二版（BDI-II）、陳氏網路成癮量表（CIAS）、及中文版尋求再保證量表（CRSS），並於四週後填答BDI-II、CIAS、及現實/網路尋求再保證量表。結果：（1）控制初始網路成癮傾向後，初始憂鬱仍能顯著預測後續網路成癮。（2）尋求再保證風格能顯著預測網路成癮，且此一關係受到初始憂鬱之調節。（3）初始網路成癮能調節尋求再保證風格與現實/網路尋求再保證後果之關係，然而初始憂鬱並無調節效果。（4）現實/網路尋求再保證後果皆能中介尋求再保證風格與後續症狀之關係。（5）憂鬱與網路成癮形成模式僅獲部分支持，考量初始症狀後，現實/網路尋求再保證後果無法顯著預測後續症狀。討論：本研究將依據結果探討尋求再保證於憂鬱與網路成癮之形成路徑中所扮演的可能人際歷程，接著針對不符合原先假設的研究結果提出可能解釋，並依序闡述本研究結果之貢獻、臨床意涵、限制以及未來研究方向。OBJECTIVE: Previous studies have demonstrated that depression is the most frequently reported psychiatric symptom comorbid with Internet addiction. However, these studies were mostly with cross-sectional design and insufficient to clarify the temporal sequence of the psychopathology of these two problems. Hence, the current study aimed to examine the path from depression to Internet addiction with a prospective design. With respect to progress in technology science, interpersonal activities in Internet become more popular and indispensable in people’s lives. An alternative interpersonal approach is necessary to understand the development of depression and Internet addiction in this digital era. The current study explored whether reassurance-seeking style, an interpersonal tendency for eliciting other’s rejection and deteriorating depressive symptoms proposed by Joiner, Alfano, and Metalsky (1992) conjoining Coyne’s (1976b) interpersonal model of depression, may serve as a common risk factor for the development of depression and Internet addiction. Moreover, this study further tested the mediation role of offline/online reassurance-seeking outcomes in the path to depression and Internet addiction. METHOD: We recruited a valid sample of 181 adults (43.1% Male, 56.9% Female, age range = 20-39 years old) via web advertisement. At Time 1 (T1), participants were asked to fill out the Chen Internet Addiction Scale (CIAS), Beck Depression Inventory-II (BDI-II), and Chinese Reassurance-Seeking Scale (CRSS). At Time2 (T2, 4 weeks later), the CIAS, BDI-II, and Offline/online Reassurance-Seeking Scale were assessed. RESULTS: 1) After controlling T1 Internet addiction symptoms, T1 depressive symptoms still significantly predicted T2 Internet addiction symptoms. 2) Reassurance-seeking style significantly predicted T2 Internet addiction symptoms, and such correlation was moderated by T1 depressive symptoms. 3) T1 Internet addiction symptoms moderated the relationship between reassurance-seeking style and offline/online reassurance-seeking outcomes respectively, while T1 depressive symptoms did not serve as a moderator. 4) Offline/online reassurance-seeking outcomes mediated the relationship of reassurance-seeking style and T2 depressive as well as Internet addiction symptoms. 5) The model of path to depression and Internet addiction was partially supported. In specific, offline/online reassurance-seeking outcomes could not predict the followed-up symptoms while taking initial symptoms into account. DISCUSSION: Based on the above findings, the interpersonal process of reassurance seeking was discussed to elucidate the development of depression and Internet addiction. Finally, applications, clinical implications, limitations and future directions of the study were further addressed
Semantic processing as a neuro-cognitive endophenotype of schizophrenia
No full text目的：思覺失調症是我們所知遺傳性最高的精神疾患之一。在病理研究中，學者提出內生表現型（Endophenotype）的概念，用以測量外顯病徵與基因訊息之間細微的神經生物╱認知表現型，進一步對病理有更深的了解。混亂的語言╱行為是思覺失調症的五大症狀之一，但是，語言處理缺損與思覺失調症基因的關係尚不清楚，因此，本研究藉由檢驗思覺失調症病人、未患病手足以及一般未患病者的語意處理表現和其神經生理基礎，探討語意處理和思覺失調症基因的關係。方法：利用功能性磁振造影（functional Magnetic Resonance Imaging）技術檢驗思覺失調症病人（平均年齡 為32.9，標準差為5.1）組、未患病手足組（平均年齡為34.0歲，標準差為6.6歲）、一般正常人組（平均年齡為33.0，標準差為4.9）的語意處理歷程。三組（各29人）的智力分數、年齡沒有顯著差異，皆慣用右手。在磁振造影掃描的同時，受試者要完成中文語意聯想作業，亦即螢幕上出現的前後兩個中文字有沒有意義關聯。此外，將腦部活動大小程度與魏氏智力測驗第三版（WAIS-III）、思覺失調症正負性症狀量表（PANSS）作相關，以探討大腦活動與認知功能╱病人症狀之間的關聯。結果：在語意判斷作業中，病人組的正確率、反應時間都較手足組為低，而手足組的表現與一般正常人組則沒有顯著差異。在進行中文語意處理時，病人組在左腦額下迴（IFG，BA45）、左腦顳中迴（MTG，BA 21）的活動較手足組、一般正常人組為高；另一方面，一般正常人組在左腦頂下小葉（IPL，BA39）的活化程度顯著地較病人組與手足組為高。此外，病人組在左側額下迴的活化程度與症狀量表思緒混亂（conceptual disorganization）分數呈正相關，控制組在左側顳中迴的活化程度與魏氏智力測驗中記憶廣度的分數呈負相關。結論：本研究發現思覺失調症病人與手足在語意處理時不同的神經生理機制。病人左側額下迴與顳中迴的活化程度較高，顯示他們在進行語意判斷作業時，需要花費更多精力來提取與儲存語意訊息。其中，病人左側額下迴的活化與病人思緒混亂程度呈正相關，顯示隨著症狀的嚴重性，此區域的過度活躍程度會更加明顯，而一般正常人顳中迴的活化程度較低，此處的活化又與魏氏智力測驗的記憶廣度分數呈現負相關，顯示一般正常人的記憶廣度越高，在語意表徵的儲存不需花費太多資源，病人組則沒有觀察到此一相關。另一方面，一般正常人進行語意測驗時在左側頂下小葉的活化程度較高，這個區域與跨感官語言資訊整合、空間注意力與自我概念的訊息應用有關，顯示病人和手足在進行語意聯想判斷時，可能運用不同的策略。本研究區別出語意處理時病人獨特的神經機制，與疾病狀態有關，同時，也發現手足與病人相似的神經機制，支持語意處理的部分神經機制受到與基因遺傳影響，是思覺失調症的一種內生表現型。Introduction: Schizophrenia is characterized as a highly heritable disorder. Endophenotypes have been proposed to seek for measurable components between symptoms and genotype in schizophrenia. Disorganized speech/thought is one of the core symptoms of schizophrenia. These symptoms are related to the loosening association among concepts seen in patients with schizophrenia. However, whether semantic association is an endophenotype of schizophrenia remains unclear. We aimed to investigate the underlying neural mechanism of semantic processing in patients with schizophrenia, their unaffected siblings, and healthy controls. Methods: Functional magnetic resonance imaging (fMRI) was used to assess patients with schizophrenia (mean age = 32.9 years, SD = 5.1), their siblings (mean age = 34.0 years, SD = 6.6), and healthy controls (mean age = 33.03 years, SD = 4.9). The three groups (n = 29 each) were matched in IQ, age, and handedness (all right-handed). Participants were instructed to judge whether two Chinese characters were related in meaning while brain activation patterns were recorded. In addition, the magnitude of brain activation was correlated with scores of the WAIS-III and Positive and Negative Syndrome Scale (PANSS) to examine the relationship between brain activity and cognitive functions/symptoms of schizophrenia. Results: In the semantic judgment task, the patients showed lower accuracy rate and longer reaction time than the siblings. However, there was no difference in behavioral performance between siblings and controls. In addition, the patients showed greater activation in the left inferior frontal gyrus (IFG, BA 45) and the left middle temporal gyrus (MTG, BA 21) as compared to the siblings and controls. In contrast, the controls showed greater activation in the left inferior parietal lobule (IPL, BA 39) as compared to the other two groups. Furthermore, there was a positive correlation between the index of conceptual disorganization in the PANSS and left IFG activation in patients, as well as a negative correlation between the Digit Span score in the WAIS-III and left MTG activation in controls. Conclusions: This study reveals different biological mechanisms of semantic processing in patients and their siblings. The patients produced greater activation in left IFG/MTG, suggesting that they need more effort to retrieve semantic information and search relevant semantic representations during semantic judgments. Relative to the controls and siblings, greater activation in the patients may be treated as a state marker of schizophrenia. Moreover, the patients produced less activation in left IPL. This region is involved in higher level linguistic information integration, spatial-attentional network, and self-perception. This difference indicates that the siblings and patients may be applying a different strategy when doing the semantic judgment task. Relative to the controls, greater activation in the patients and siblings may be treated a trait marker of schizophrenia regarding semantic impairments
Design, Synthesis, and Characterization of Small-Molecule Materials for Organic Solar Cells
No full text有機太陽能電池被視為低成本及低環境汙染的永續性電力來源。而電洞型有機材料應用於有機太陽能電池中做為電子予體在近年來發展迅速。近來小分子有機太陽能電池的元件表現已逼近高分子有機太陽能電池的成果，顯示其有相當大的潛力取代矽基太陽能電池成為下一世代的光伏電池。本篇研究著重於有機太陽能電池中，具予體-受體-受體(D-A-A)結構的小分子電子予體材料，其設計開發、合成及分子特性的鑑定。此外，藉由探討D-A-A電子予體中各單元體的組成和特性，可得知化學結構、分子性質和元件表現之間的關係。文中將於第一章介紹小分子電子予體材料的設計原理，並將其應用在D-A-A架構的電子予體中。而其他章節將介紹各個功能性單元體於D-A-A電子予體中對於分子特性的影響，包括:推電子基團(D)對小分子的電化學性質和分子立體障礙的影響。利用不對稱合成建構各種D-A-A電子予體的中間拉電子基團(A)，並應用在有機太陽能電池中。修改D-A-A電子予體的末端拉電子基團(A)進行分子能階的調控，並透過簡單快速的方法來合成電子予體以實現永續化學的理念。藉由各個單元體在D-A-A電子予體中的排列組合，我們可以控制有機小分子電子予體的各項性質，並且探討及連結分子結構和有機小分子太陽能電池效率表現的關係。rganic Solar Cells (OSCs) have been regard as cost-effective and promising sources of electricity with environmentally benign sustainability. The p-type organic materials as electron donors for OSCs were developed prosperously in the past few decades. Recently, the performance of small-molecule organic solar cells (SMOSCs), has approached the results that organic polymer solar cells achieved, demonstrated high potential as alternatives to silicon-based solar cells for the next generation of power sources in photovoltaics (PV). The research in this dissertation was focus on the design, synthesis, and characterization of small-molecule materials with donor-acceptor-acceptor (D-A-A) molecular configuration for OSCs. Furthermore, each part of composition in D-A-A donors was investigated to develop the relationship between the structure-property and photovoltaic performance. In this dissertation, design principles for small-molecule materials were illustrated in Chapter 1 and contributed into the construction of D-A-A organic donors. Further discussion of each functional moieties in D-A-A organic donors along with various fundamentality-influence were organized including electronic and steric effects of electro-donating units, the novel asymmetric strategies for diversity of middle electron-withdrawing units in OSCs, the manipulation of energy levels through the modification of terminal electro-withdrawing units and their application in one-step synthesis of D-A-A organic donors for sustainable chemistry. Through the permutation and combination of building block in the D-A-A organic donors, we could control the intrinsic properties of D-A-A organic donors that were explored to connect the molecular structures with the performance of SMOSCs
Investigating the in vivo role of Carboxyl-terminal Domain of Wntless protein in Zebrafish embryonic development
No full textWnt ligand是一個在多細胞生物中被廣泛使用之蛋白質訊息分子。Wnt所誘發的訊息傳遞路徑被廣泛使用在眾多生物現象之中，包含胚胎早期發育、幹細胞多型性維持和細胞癌化。對於Wnt訊息所引發之反應已有廣泛的研究，但關於Wnt如何被製造和如何自細胞釋放等的詳細資訊仍有所不足。Wntless蛋白被報導負責將Wnt由高基氏體運送至細胞膜的攜帶蛋白質，Wntless存在與否對於多數Wnt之分泌皆有重大影響。透過研究Wntless，我們即可從側面探索Wnt如何在細胞中被輸送和釋放。儘管數個Wntless的功能性區段已被報導，但Wntless羧基端區段在斑馬魚中所扮演之功能仍然尚未釐清。在本實驗室先前研究中推測Wntless的羧基端150個胺基酸殘基對於其功能扮演重要角色。而在本研究中，我進一步針對Wntless最末端49個胺基酸區塊設計切除版本，並且將受部分切除的mRNAs以顯微注射的方式使其表現在Wntless突變的斑馬魚胚胎中。實驗組中，表現末端缺乏的Wntless和單獨只有最末端兩種版本皆無法拯救wls突變之斑馬魚胚胎，據此我推測Wntless羧基端為其生物功能必須之區段。此外，我使用特定辨識羧基端之抗體來進行免疫螢光染色，發現單獨只剩羧基端的切除版本和切除中間第221至420胺基酸區段的Wntless之細胞內分布與全長的Wntless不同。據此我推測這兩個切除版本的切除區段皆為Wntless在細胞之中被正確運送所必須。Wnt is a secreted ligand and involved in numerous cell-cell signaling processes, especially in embryo development and tissue homeostasis. Comparing to the understanding of the responding signaling in Wnt-receiving cells, the sorting and secretion of Wnt in Wnt-producing cell is less clear. Wntless (Wls, also known as Gpr177 in mammal) plays a crucial role in carrying Wnts from Golgi to plasma membrane. Although several important functional motifs of Wls have been identified, whether the carboxyl-terminal domain of Wls is functional in zebrafish embryonic development is unknown. I have evaluated the abilities of different truncated Wls proteins in rescuing the inner ear and jaw cartilage defects of wls mutants. I found that neither the carboxyl-terminal 49 amino acids deleted form nor the form containing only the carboxyl-terminal 49 a.a rescue the defects of wls mutants. These data indicate that the carboxyl terminal 49 amino acids are important for Wls function in modulating Wls-mediated development in zebrafish embryo. In addition, utilizing antibody against Wls carboxyl-terminal 49 amino acids, I found the subcellular location of the truncated Wls containing only the carboxyl-terminal 49 a.a or carrying a.a. 221-420 deletion is distinct from endogenous Wls. I suggest these deleted region are both required for Wls subcellular sorting
An anatomical study of cerebellum projection to anterior cingulate cortex through thalamus
No full text小腦除了在運動功能上扮演重要角色，近期行為及電生理研究也發現小腦參與了認知和情緒等功能，但在解剖上的證據較不明確。本研究在大鼠腦中注射神經追蹤劑，來觀察小腦及和情緒功能高度相關的大腦邊緣系統之間的連結。本實驗分為四個部分：(1)在大鼠小腦深部核(deep cerebellar nuclei, DCN)注射順行性神經追蹤劑;(2)在大鼠視丘中央部位注射反行性神經追蹤劑;(3)在大鼠前扣帶迴皮質區(anterior cingulate cortex, ACC)注射反行性神經追蹤劑;(4)同時在大鼠小腦注射順行性神經追蹤劑，並在大腦邊前扣帶迴皮質區注射反行性神經追蹤劑。使存活一段時間後，將動物犧牲灌流並將腦固定後取出，以冷凍切片並進行觀察。在此研究中發現:(1)小腦除了投射至腹前側核(ventral anterior thalamic nucleus, VA),腹外側核(ventrolateral thalamic nucleus, VL),腹內側核(ventromedial, VM)等運動相關核區，也會投射到內背側核外側部分(lateral part of mediodorsal thalamic nucleus, MDL),中央旁核(paracentral thalamic nucleus, PC),中央外側核(centrolateral thalamic nucleus, CL),中央內側核(central medial thalamic nucleus, CM)等位於視丘的核區，其中以齒狀核(dentate nuclei, DN)的投射最多。(2)靠近尾端的內背側核, 板內側核(intralaminar nuclei, ILN)等視丘核區傾向投射到靠近頭側的前扣帶迴皮質區，而較頭側的視丘核區則會投射到靠近尾端的前扣帶皮質區。(3)在小腦及前扣帶迴皮質區分別注射順行及反行性的神經追蹤劑實驗中，發現在小腦齒狀核及中間核(interposed nuclei, IN)注射追蹤劑的大鼠中，可以在視丘內背側核外側部分,中央旁核,中央外側核等區域發現被標定的神經細胞被從小腦投射而來的軸突末端包圍。說明小腦中神經元可能通過丘腦中的這些核區作為中繼站進而和前扣帶迴皮質區進行連結與功能協調。本結果在解剖上提供小腦在認知、情緒等非運動功能上也扮演了協調的可能。Cerebellum has long been thought as a main area for motor executive control. Recent studies of electrophysiology and behavior reveal that cerebellum also participates in cognitive and emotional functions. However, there is still no sufficient anatomical evidence. The study includes four parts: we (1) injected anterograde neuronal tracer in the rat deep cerebellar nuclei (DCN); (2) injected retrograde tracer in the mid thalamus; (3) injected retrograde tracer in anterior cingulate cortex (ACC); (4) simultaneously injected anterograde tracer in the DCN and retrograde tracer in ACC. After several days of survival, the animal was sacrificed for perfusion and the brain was fixed and removed for further frozen section. The results show: (1) Except for ventral anterior thalamic nucleus (VA), ventrolateral thalamic nucleus (VL) and ventromedial thalamic nucleus (VM), cerebellar also projects to non-motor nuclei, such as lateral part of mediodorsal thalamic nucleus (MDL), paracentral thalamic nucleus (PC), centrolateral thalamic nucleus (CL) and central medial thalamic nucleus (CM), and dentate nuclei (DN) is the main output. (2) The retrograde tracing of ACC injection of fluoro-gold shows a tendency that rostral medial thalamus preferentially projects to A2 and caudal medial thalamus to A4 level of ACC. (3) In MDL, PC, and CL, many retrograde tracer labeled neurons can be seen and anterograde tracer labeled axon fiber and boutons around those neurons. Our results indicate that the cerebellum may have connections with anterior cingulate cortex through mediodorsal thalamic nucleus, paracentral nucleus, or central lateral nucleus and provide anatomical data showing the role of emotional coordination by the cerebellum
Integrative Quantitative Proteomics and Phosphoproteomics Reveal the Regulatory Role of ZNF322A in Lung Cancer A549 Cells
No full text鋅指蛋白322A (ZNF322A)屬於C2H2型鋅指蛋白家族並擁有轉錄因子的功能。近年的研究指出，在肺癌病患檢體中，ZNF322A有過度表現的現象，可能為肺癌的致癌基因之一，然而，ZNF322A調控的網路尚未被徹底解析。在本研究中，我們結合了定量蛋白質體學及磷酸化蛋白質體學的方法，分析ZNF322A在人類肺腺癌細胞株A549的調控網路，利用羥基酸修正金屬氧化物層析(hydroxy acid-modified metal oxide chromatography, HAMMOC)、相對定量同位素標定(isobaric tag for relative and absolute quantitation, iTRAQ)及液相層析與串聯式質譜儀(LC-MS/MS)的技術，我們發現2754個磷酸化位置對應到1822個磷酸肽及976個磷酸蛋白上，其中共有138個磷酸化位置受ZNF322A調控。比對先前的蛋白質體資料並利用功能富集、生物網路和磷酸化基序列分析等生物資訊學的方法，我們發現ZNF322A可能參與RNA加工及細胞週期等調控，且熱休克蛋白27 (HSP27)的Ser82磷酸化位置有顯著的表現量上升，並與轉錄起始因子eIF2α一同參與啟動未摺疊蛋白反應(unfolded protein response)，另外，IRS1 Ser1101磷酸化位置的表現量上升可能參與調控葡萄糖的運送，結果指出HSP27與IRS1為ZNF322A下游的調控磷酸化蛋白。本研究對於ZNF322A在人類肺癌細胞中的分子調控機制有更深入的了解，期望能對肺癌的治療發展有所貢獻。ZNF322A is a transcription factor that belongs to C2H2-type zinc finger protein family. Recent study revealed that ZNF322A is a potential oncogene in lung cancer patients. However, the network regulated by ZNF322A was still unknown. In this study, we integrated quantitative phosphoproteomic and proteomic analyses for ZNF322A-silencing lung cancer A549 cells. Hydroxy acid-modified metal oxide chromatography (HAMMOC) phosphopeptide enrichment method, and isobaric tag for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS were applied. We identified 2754 phosphosites corresponding to 1822 phosphopeptides and 976 phosphoproteins, among these, 53 phosphosites were upregulated and 85 were downregulated in siZNF322A treated cells. Quantitative iTRAQ LC-MS/MS proteomics reveals the proteome profile in ZNF322A-silencing A549 cells, and 1108 proteins were identified. By bioinformatics approaches including functional enrichment, network and phosphorylation motif analyses, the results indicated that ZNF322A might regulate several biological processes, such as RNA processing and cell cycle. Phosphorylation of HSP27 Ser82 and IRS1 Ser1101 were significantly upregulated upon ZNF322A-silencing and participate in the regulation of unfolded protein response and glucose uptake. Our study provides a new insight for further investigation of protein phosphorylation status in ZNF322A-mediated lung cancer cells
Acid-induced ERK phosphorylation in Cortical Principle Neurons & Excitatory Synaptic Plasticity in RAIC in Mice?
No full text為了瞭解慢性肌肉疼痛的相關機制，本研究援引Sluka等人在2001年所發表的酸誘發慢性肌肉疼痛模型 (AIMP 模型) 作為研究工具，此模型可藉由在左腿腓腸肌重複注射酸性食鹽水而在雙側腳掌都誘發出長期的痛覺敏感現象。一般相信中樞敏感現象與酸誘發之慢性肌肉疼痛的機制相關，先前研究亦已指出脊髓、視丘與杏仁核等區域的角色，但大腦皮質所扮演的角色仍然不清楚，包括了到底是興奮性神經元或是抑制性神經元會在慢性肌肉疼痛的建立機制中被活化？本研究主要分為兩大部分：第一部分是型態實驗，著手於辯明在大腦皮質中在酸痛模型下活化的細胞種類；第二部分是電生理實驗，聚焦於前端無顆粒狀島葉(RAIC)的興奮性突觸可塑性之探討。 第一部分使用磷酸化細胞外信號調節激酶 (pERK) 來標定被活化的細胞，並結合雙重標定或三重標定之免疫染色方法確定其細胞種類。其中，NeuN 被用來標記神經細胞；Calmodulin kinase II （CaMKII) 被用來標定興奮性細胞；GAD-GFP 與 VGAT-tdtomato 兩品系之基因轉殖鼠被用來標定抑制性細胞。結果顯示，在重複注射第二針酸之後，pERK的活性在前扣帶皮質與島葉都有增加，且表現pERK的細胞幾乎全都是神經元而非神經膠細胞，且重要的是，pERK表現於興奮性神經元，而幾乎不表現於抑制性神經元。 第二部分使用全細胞鑲嵌技術紀錄前端無顆粒狀島葉的第五層錐狀細胞，並電刺激其第二/三層的位置來誘發出興奮性突觸後膜電位(eEPSPs)。藉由高頻電刺激的方式，可以誘導出長期增益現象(LTP)，此長期增益現象與高頻電刺激的重複次數相關，並與 NMDA 受器相關。除此之外，由於高頻電刺激的重複次數過少將不足以誘發長期增益現象，因此我們假定有誘發長期增益現象的閾值存在於前端無顆粒狀島葉。 結合以上結果，包括ERK在慢性疼痛模型當中活化於興奮性神經元，加上在正常小鼠中前端無顆粒狀島葉的興奮性神經元可以展現突觸可塑性，所以我們認為(前端無顆粒狀島葉的)興奮性神經元在慢性酸痛模型中扮演了重要角色，這也提供了關鍵點以供纖維肌痛症的相關研究。In order to understand the mechanism of chronic muscle pain, the acid-induced muscle pain animal model (AIMP model) established by Sluka et al. (2001) was introduced. Bilateral widespread long-term hyperalgesia was reproduced by repeated acidic saline intramuscular injection into left gastrocnemius muscle. It was believed that central sensitization contributed the acid-induced muscle chronic pain and previous studies had discussed on the spinal cord or subcortical areas; however, the role of cortical areas was still unclear, including whether the nociceptive neurons was excitatory or inhibitory in the developing of chronic muscle pain. The study was interested in the cell-type of nociceptive neurons and synaptic plasticity within cortical areas, especially the rostral agranular insular cortex (RAIC). This study consisted of two main experiments, one was investigating the cell-type of nociceptive neurons in the cortical areas within AIMP model; the other was to examine whether a synaptic plasticity could be elicited in rostral granular insular cortex.
First, the phosphorylated extracellular signal-related kinase (pERK), a biological activity and nociceptive marker, had been examined after the second acid injection. The pERK-IR cells were elevated in the bilateral anterior cingulate cortex (ACC) and insular cortex (IC), and combined with double labeled pERK-NeuN immunostaining, showing that the pERK-IR cells were almost all (at least 96%) neurons. Next, calmodulin kinase II (CaMKII), a general marker for pyramidal cells, were used for labeling excitatory principle neurons; in the other way, GAD-GFP mice and VGAT-tdtomato mice were also used for labeling GABAergic neurons. Triple-labeled of pERK&CaMKII&GAD (or VGAT) showed that around 40% pERK-IR cells were CaMKII-IR principle neurons, and rarely pERK-IR cells were GABAergic interneurons in the ACC and IC.
Second, whole-cell patch clamp was done on the RAIC layer V pyramidal cell and evoking EPSPs by a local stimulation on RAIC layer II/III. Under high frequency stimulus with 100Hz in one second and repeated five or seven times (repeated times defined as train number ), a long-term potentiation of EPSP was elicited. The LTP on RAIC is train number-dependent and NMDA receptor-dependent. Furthermore, it was suggested that a threshold as train number of three within the RAIC for establishing LTP.
In conclusion, the excitatory pyramidal cells played the critical roles in the ERK activation and the synaptic plasticity, which helped us much understand the mechanism of chronic muscle pain, and might provide a hint on the research of fibromyalgia
A Sociocultural Approach to The News-making of a Major Natural Disaster: Exploring on TV News Works of Typhoon Morakot in Taiwan
No full text 本論文之研究目的是詮釋和探索臺灣重大自然災難新聞產製的社會文化意涵，藉此釐清新聞工作者在充滿不確定性的情境脈絡下如何經驗專業。在研究方法上，本研究主要透過深度訪談29位電視新聞工作者的勞動經驗和職業詮釋，輔以次級資料來進行分析。 本論文有兩個主要的研究問題，分別在四、五兩章進行分析和回應。首先在第四章的分析討論中，透過分析社會結構、電視新聞的公共論述以及電視新聞工作者的實作經驗，本論文探索分析重大自然災難的電視新聞工作是如何鑲嵌在商業結構所主導的社會文化脈絡中。如此也有利於本研究歸納兩點研究發現：第一個發現是，在例行的新聞產製過程之中，由結構力量所引導、轉變的新聞產製規範被新聞工作者遵循或反抗，以至於讓例行的新聞產製文化成為依循結構邏輯的文化實作；第二個發現是，臺灣新聞產製文化的發展過程，主要受到市場經濟力主導，這也導致了臺灣的新聞產製文化，普遍缺乏客觀專業主義的文化實作。 針對第二個研究問題，本論文在第五章中進一步分析電視新聞工作者的職業觀、產製情境以及處於災難風險情境下所形成的反思經驗、具體作為。研究發現，災難新聞產製過程中的各類新聞工作者，普遍經歷高度不確定性以及惡劣的勞動條件。災難情境迫使各類新聞工作者必須要有更多的臨機反應，以彈性的方式來建構出各種因應現實狀況的文化腳本。值得注意的是，依據職業認同方向（社會責任或商業利益），以及反思行動方向（追求公信或者為自利）的影響，雖然可能形成八種災難新聞產製的文化腳本，然而在八八風災的個案之中，「追求客觀平衡報導」和「服膺災難管理」這兩種文化腳本是未被實踐的。 在最後一章的總結與討論中，本論文根據上述得以指出，在非災難時刻，新聞產製常是透過常規中介結構力量，讓新聞工作者能夠在例行的新聞產製分工之中，在一種共識和共享的象徵系統下實踐他們的新聞工作，最終展現出一種回應特定社會結構所形成的職業社群期待，形成「務實」的新聞職業表現。弔詭的是，這種「務實」的表現卻偏離了社會對於新聞專業的想像和期待。 反應在八八風災這個重大災難的新聞產製文化上，正因為缺乏「追求客觀平衡報導」和「服膺災難管理」這兩項文化腳本，使得災難新聞產製的文化實踐，無法滿足社會和災難管理單位對於災難新聞的期待與需要，因而造成了社會各界對於臺灣災難新聞的不滿與批判。這樣的發現也適度解釋了，何以近年來臺灣電視新聞業在重大事件中會不斷遭受社會批判，同時逐漸喪失其專業地位。 最後，本論文以災難新聞工作者的勞動經驗為本，反思臺灣重大災難新聞產製文化所內涵的問題與矛盾，並提出更貼近風險社會觀的新聞產製文化的轉型之建議。 This thesis aims to explore the social and cultural implicaitons of news production in face of major natural disasters in Taiwan. Through analyzing the professional views and role identities shared by news workers and how they produce news and commit to journalism under such cultural background, this research attempts to clarify the implications and practical effects of the culture of disaster news production. In terms of methodology, depth interviews with 29 TV news workers are conducted to learn their work experience and occupation interpretation, and corresponding data analysis is made to provide statistical support. There are two main research questions in this study, which are analyzed and answered in Chapter Four and Chapter Five respectively. In Chapter Four, based on the analysis of the public understanding of social structure and television news as well as the practical experience of TV news workers, the research diachronically reviews how television journalism is connected to the specific social-cultural contexts. Correspondingly, two research findings are concluded here. First, during the conventional course of news production, relevant norms guided and transformed by the power of structure are either accepted or resisted by journalists. As a result, the conventional news production culture turns into some cultural practice following the structural logic. Second, the development of Taiwan’s news production culture is mainly dominated by economic powers, which leads to a general lack of objective professionalism in the cultural practice of Taiwan’s news production. To answer the second research question, this research discusses in Chapter Five the professional views of television journalists, relevant production situations, as well as their reflection experience and concrete actions in face of disaster risks. It is found that journalists in the process of disaster news production generally face high degree of uncertainty as well as poor working conditions. Disaster situations require that journalists must have the abilities to adapt themselves to the changing circumstances and flexibly construct various cultural scripts according to the practical conditions. It is important to note that there are eight types of cultural scripts in disaster news production according to professional identities (social responsibility or business interests) and reflection actions (pursuit of public trust or self-interest). However, in the case of Typhoon Morakot, cultural scripts of “pursuing objective and balanced reporting” and “complying to disaster management” are not practiced. It is concluded in the last chapter that a research from the cultural perspective is helpful for researchers to explore how news workers begin learning from practicing after they enter the TV news field and learn to complete their duties in work field. During the non-disaster period, news production culture enables news workers to practice their jobs under routine division of news production in the symbol system of consensus and sharing, so as to eventually represent a “practical” journalism performance that responds to occupational community expectations. Strangely, however, such “practical” performance is deviated from the imagination and expectation of the society for journalism. With regard to cultural scripts of news production in the serious case of 8.8 windstorm disaster, due to the lack of cultural scripts “pursuing objective and balanced report” and “complying to disaster management”, the cultural practice of disaster news production failed to satisfy the expectation and demand of disaster news from the society and disaster management units, thus causing discontent and criticism from all walks of life on Taiwan’s disaster news. Such a finding also partly explains why Taiwan’s television journalism has been constantly subject to social criticism in major events and gradually losing its professional status in recent years. Finally, the dissertation discusses the problems and conflicts hidden in the culture of Taiwan’s major disaster news production in accordance with disaster journalists’ work experience, and offers suggestions for the transformation of news production system that toward risk society
The brain activity changes of tactile allodynia and the analgesic effect of gabapentin in the neuropathic rats
No full text神經病變性疼痛為體感覺系統因疾病或損傷所產生的疼痛，在臨床上不易治療，因對其病理機制的了解仍有限。觸感痛是神經病變性疼痛的主要症狀，特徵為對正常人無痛的觸覺刺激卻會引發病人疼痛。目前對觸感痛的研究著重在周邊感覺神經及脊髓背角的功能性變化，而腦部在觸感痛時扮演的角色仍待了解。Gabapentin (GBP)是臨床上治療神經病變性疼痛的主要藥物，但其在腦中的作用位置還不清楚。本論文使用正子造影及免疫組織化學方法，研究神經損傷大鼠腦部在觸感痛狀態下的功能性變化，及GBP在腦部可能的作用位置。我們將大鼠坐骨神經的分支脛神經及腓總神經結紮後切斷，保留腓腸神經完整。神經損傷大鼠很快發展出自發性疼痛、觸感痛及痛覺過敏等現象。我們比較神經損傷大鼠在觸感痛狀態下腦部的葡萄糖代謝率及神經活化標誌的變化，以及給予GBP止痛後的改變。由正子造影的結果顯示，觸感痛會使神經損傷大鼠腦部的島狀皮質前側、丘腦及小腦的代謝率增加，而給予GBP止痛可回復丘腦及小腦的代謝率，並使前額葉皮質及前扣帶迴皮質代謝率降低。由免疫組織染色的結果顯示，磷酸化細胞外訊息調節激酶(pERK)及神經活化蛋白(c-Fos)在神經損傷大鼠的前額葉皮質、前扣帶迴皮質及島狀皮質前側等邊緣皮質有大量的表現。神經損傷大鼠腦中pERK細胞在前額葉皮質及島狀皮質前側較對照組有顯著增加，而c-Fos細胞則在前額葉皮質較對照組有顯著增加；經由給予GBP止痛後，這些大量表現的細胞顯著的減少。我們更進一步確認在腦中這些表現pERK或c-Fos的細胞是神經元，而非星狀膠細胞。由本研究的結果可知，觸感痛在神經損傷大鼠腦中主要改變了邊緣皮質的細胞活性，而GBP在腦部的作用位置可能就是在抑制邊緣皮質的細胞活性來達成止痛作用。Neuropathic pain is caused by injury or disease of the somatosensory system. Treating neuropathic pain is difficult because its pathophysiological mechanisms are understood limitedly. Tactile allodynia, the innocuous touch-evoked pain, is one of the major symptoms of neuropathic pain patients. So far the studies of tactile allodynia are focused on the functional alterations in the primary afferents and the spinal dorsal horn neurons, however, the role of brain in the tactile allodynia is still unclear. Gabapentin (GBP) is a first-line analgesic to treat neuropathic pain, but its action sites in the brain remains to be disclosed. In this thesis, we used positron emission tomography (PET) and immunohistochemical methods to investigate the functional alterations in the brain of neuropathic rats under allodynic state, and the action sites of GBP in the brain. We used the spared nerve injury (SNI) model of neuropathic pain. In the SNI model, the tibia and common peroneal nerves of the sciatic nerve were ligated and cut, and leaving the sural nerve intact. The nerve-injured rats developed spontaneous pain, tactile allodynia and thermal hyperalgesia. Then we compared the glucose metabolic rate and neuronal activation markers in the brain of neuropathic rats under allodynic state, and the effect of GBP. The PET results showed glucose metabolic rates increased in the anterior insular cortex (IC), thalamus and cerebellum after nerve-injury, and GBP treatment reversed the increases in the thalamus and cerebellum, and decreased the glucose metabolism in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). The immunostaining results showed an abundant expression of pERK and c-Fos in the mPFC, ACC and anterior IC. For pERK study, the pERK-positive cells in the neuropathic rats increased significantly in the mPFC and IC than control rats. For c-Fos study, the c-Fos-positive cells in the neuropathic rats increased significantly in the mPFC than control rats. After GBP treatment, the increased expression of pERK and c-Fos decreased significantly. We also demonstrated the pERK- or c-Fos-positive cells were neurons, not the astrocytes. According to our studies, the tactile allodynia affect the neuronal activities in the limbic cortices of neuropathic rats, and the effect of GBP was to suppress the activation of limbic cortices
Stock Analyses on the Short-head and Buccaneer Anchovies in the Waters around Taiwan
No full text魩鱙漁業為臺灣周邊水域重要小型漁業，其捕獲物種主要由日本鯷、異葉公鯷與刺公鯷三種鯷科仔稚魚所組成。由2002年到2012年的豐度組成得知此兩種仔稚魚豐度存在年間及季節間變異。藉由漁獲組成之時間別及海域別間差異分析，可推測異葉公鯷與刺公鯷乘著台灣南面洋流添入沿岸漁場，且此兩種魚洄游至產卵場時間及深度相當；然而是否源自南方單一系群或多個系群仍有待釐清。本研究主旨為分別探討此二物種之仔稚魚如何匯入臺灣海域，以完成其生活史之成育階段，並且定義其單位系群。究明其南方來源有助漁業管理之實務及理想性，可達成沿岸魩鱙魚獲資源永續利用之目標。 本分析所需樣本得自2010至2013，空間區分為三個分立成育場，分別為臺灣東北、西北及西南海區。年別樣本將反應添入年級群強度，並分為春季與秋季兩個季節群。族群性狀特徵以外形與分子差異分別定量。外形區分由族群多變數形態分析檢定，而分子差異由粒線體中胞色素b為族群標記，由完整三因子變方分析結果顯示系群關係。 統計分析於外形性狀判別中，異葉公鯷樣本呈現春秋兩季節獨立分群，此結果於基因序列分析再次被驗證，可得知異葉公鯷仔稚魚源自兩個獨立母魚群體，並且於不同季節時各自匯入沿岸漁場；統計結果顯示刺公鯷則無顯著分群現象，應為單一系群。此分群現象與臺灣周遭洋流之季節交替系統相對應，夏季時棲息於南海西岸的異葉公鯷藉由南海海流到達台灣成育場，而冬季時東北季風增強，中國沿岸流順勢強度提升，導致南海暖流方向轉為順時針，此時南海東岸的異葉公鯷乘著黑潮支流得以到達台灣，因此可見春秋兩分立季節群；相反地，匯入台灣的刺公鯷主要源自菲律賓群島東岸之太平洋，整年由黑潮遷移至台灣繁殖，故並無系群分群現象。 目前臺灣地區全區適用之魩鱙管理，基於刺公鯷與日本鯷皆屬單一系群，沿岸魩鱙漁業以單一系群管理之規範應屬合理，然而多系群的異業公鯷受台灣周遭表層流影響甚巨，受氣候變遷(例如聖嬰現象)改變洋流系統，將連動影響異葉公鯷添入漁場的相對豐度，因此在長期管理上應納入氣候變遷因子，以達魩鱙漁業永續經營之目標。Bua fisheries are commonly practiced in the coast of Taiwan by artisanal fishermen. Annual abundance of the Bua resources varied, and two congener anchovies are main catch components (e.g., short-head anchovy (Encrasicholina heteroloba) & Buccaneer anchovy (E. punctifer)). Based on the fact that the catch composition varied spatiotemporally, we hypothesize that their recruitment is related with seasonal flow pattern in the southern waters of Taiwan. Nonetheless, these anchovies originated from a single or multiple sources still remain unclear. This study provides important data to improve management plan of the Bua fisheries in achieving their sustainability. To test the hypothesis, I prepared samples that obtained from 2011 to 2013, with 3 geographic nursery grounds of the northeastern (NE), northwestern (NW) and southwestern (SW) Taiwan. Population distinction was quantified by morphological shape differences and degree of molecular segregation. The shape differences reflecting phenotypic responses were analyzed by multivariate statistics. Molecular segregation showing in DNA differences were measured through mitochondrial cytochrome b gene. The results revealed that annual and spatial distinction for short-head and Buccaneer anchovies were insignificant. However, seasonal difference was detected for short-head anchovy, indicating multiple cohort might recruit to the coastal nursery grounds and the recruitment pattern can be explained by the prevailing marine current system in the vicinity of Taiwan. During summer-autumn period, short-head anchovy in the western South China Sea (SCS) migrates north with South China Sea Surface Current (SCSSC) reaching to the coasts of Taiwan. In winter-spring, the east SCS residents migrate to Taiwan due to strengthened northeast monsoon that lessens SCSSC, and promotes Kuroshio Branch Current (KBC) moving waters into Taiwan Strait. Alternating circulation driven by seasonal monsoon results in subpopulation of the short-head anchovy. Nonetheless, Buccaneer anchovy is located in east of Philippines to the Pacific Ocean side, where the geostrophic Kuroshio Current (KC) flows year round with no seasonal segregation. Currently, a unified management plan, established in 2000 is rated reasonable at present for simplicity of regulation, because single stock is found with Buccaneer and Japonicas anchovy. However, climatic changes may have effects on the flow pattern of ocean currents, and subsequently affect the recruitment of short-head anchovy. Therefore, special treatment is also needed when long-term management plan is considered