Calvin, the Church, and Displaced Persons

McKee, Elsie Ann Torch Trinity Graduate School of Theology 2010 Torch Trinity Journal Vol.13 No.2

카타리나 슈츠 첼, 이델레트 드 뷰르, 개혁주의 여성들의 결혼관과 결혼경험

엘시 안나 맥키(Elsie Anne McKee) 고신대 개혁주의 학술원 2016 갱신과 부흥 Vol.18 No.1

개신교 운동은 근대 초기의 결혼 이해에 대해서 상당히 긍정적인 영향력을 행사했으며 개혁주의 전통의 여성들은 이러한 변화에 적극 적으로 참여했다. 개신교도들은 하나님의 호의를 얻기 위한 선행으 로서의 독신을 거부했으며 결혼을 성직자를 포함한 크리스찬을 위한 이상으로 향상시켰다. 개혁주의 여성들이 그들의 신앙을 표현했던한 가지 방법은 사제들과 결혼함으로서 성직자들의 결혼을 금지했던 중세의 교회법에 항거하여 성경적 권위(예, 딤전 3장)에 대한 확신을 드러내는 것이었다. 명망이 높은 시민이었던 과거의 수녀들은 신앙에 대한 표현으로서 종교개혁자들과 결혼했다. 결혼의 이상에 대해서 개혁주의 여성들이 기여했던 둘째 방식은 그들이 가정을 꾸려 나감에 있어서 이를 그리스도를 따라감에 있어서 환대와 참여의 모델로 삼았다는 점이다. 상당한 수의 개혁주의 여성들은 그들의 신앙과 개신교 남편을 위해서 망명을 선택했다. 카타리나 슈츠 첼과 같은 자들은 그들이 사제들과 결혼하겠다는 결정과 “교모”로서 봉사를 위한 그들의 소명을 방어하는 생각을 분명하게 표현했다. 신앙과 결혼 사이에서 택일해야 하는 상황에 놓이게 되었을 때 안느 아스큐와 같은 개혁주의 여성들은 결혼을 거부함으로서 그들의 신앙적 충성심을 보여주기도 하였다. The Protestant movement had a significantly positive effect on early modern understandings of marriage, and women of the Reformed tradition participated actively in these changes. Protestants rejected celibacy as a good work to earn God’s favor and elevated marriage as an ideal for Christians, including for clergy. One way that Reformed women expressed their faith was by marrying priests, thus acting on their conviction of Biblical authority (e.g., 1 Tim. 3) over canon law which prohibited clerical marriage. Former nuns, citizens of good reputation, married reformers as expressions of faith. A second way that Reformed women contributed to the new ideal of marriage was by the ways that they managed their households, making these models of hospitality and partnership in following Christ. A number of Reformed women chose exile for their faith and their Protestant husbands. A few, like Katharina Schütz Zell, were articulate in defending their decision to marry priests and their calling to serve as “church mothers”. Some Reformed women, like Anne Askew, demonstrated their loyalty to their faith by rejecting marriage when it came to a choice between their faith and their marriages – or their lives.

MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS

Lee, Jae Keun,Shin, Jin Hee,Hwang, Sang Gil,Gwag, Byoung Joo,McKee, Ann C.,Lee, Junghee,Kowall, Neil W.,Ryu, Hoon,Lim, Dae-Sik,Choi, Eui-Ju National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.29

<P>Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by loss of motor neurons. Dominant mutations in the gene for superoxide dismutase 1 (SOD1) give rise to familial ALS by an unknown mechanism. Here we show that genetic deficiency of mammalian sterile 20-like kinase 1 (MST1) delays disease onset and extends survival in mice expressing the ALS-associated G93A mutant of human SOD1. SOD1(G93A) induces dissociation of MST1 from a redox protein thioredoxin-1 and promotes MST1 activation in spinal cord neurons in a reactive oxygen species–dependent manner. Moreover, MST1 was found to mediate SOD1(G93A)-induced activation of p38 mitogen-activated protein kinase and caspases as well as impairment of autophagy in spinal cord motoneurons of SOD1(G93A) mice. Our findings implicate MST1 as a key determinant of neurodegeneration in ALS.</P>

Quantitative Proteomic Analysis Reveals Impaired Axonal Guidance Signaling in Human Postmortem Brain Tissues of Chronic Traumatic Encephalopathy

Baibin Bi,최한필,현승재,Shengnan Sun,Ning Su,Yuguang Liu,이정희,Neil W Kowall,Ann C McKee,Jing-Hua Yang,류훈 한국뇌신경과학회 2019 Experimental Neurobiology Vol.28 No.3

Chronic traumatic encephalopathy (CTE) is a distinct neurodegenerative disease that associated with repetitive head trauma. CTE is neuropathologically defined by the perivascular accumulation of abnormally phosphorylated tau protein in the depths of the sulci in the cerebral cortices. In advanced CTE, hyperphosphorylated tau protein deposits are found in widespread regions of brain, however the mechanisms of the progressive neurodegeneration in CTE are not fully understood. In order to identify which proteomic signatures are associated with CTE, we prepared RIPA-soluble fractions and performed quantitative proteomic analysis of postmortem brain tissue from individuals neuropathologically diagnosed with CTE. We found that axonal guidance signaling pathwayrelated proteins were most significantly decreased in CTE. Immunohistochemistry and Western blot analysis showed that axonal signaling pathway-related proteins were down regulated in neurons and oligodendrocytes and neuron-specific cytoskeletal proteins such as TUBB3 and CFL1 were reduced in the neuropils and cell body in CTE. Moreover, oligodendrocyte-specific proteins such as MAG and TUBB4 were decreased in the neuropils in both gray matter and white matter in CTE, which correlated with the degree of axonal injury and degeneration. Our findings indicate that deregulation of axonal guidance proteins in neurons and oligodendrocytes is associated with the neuropathology in CTE. Together, altered axonal guidance proteins may be potential pathological markers for CTE.

SIRT3 deregulation is linked to mitochondrial dysfunction in Alzheimer's disease

Lee, Junghee,Kim, Yunha,Liu, Tian,Hwang, Yu Jin,Hyeon, Seung Jae,Im, Hyeonjoo,Lee, Kyungeun,Alvarez, Victor E.,McKee, Ann C.,Um, Soo‐,Jong,Hur, Manwook,Mook‐,Jung, Inhee,Kowall, Neil W.,Ry John Wiley and Sons Inc. 2018 Aging cell Vol.17 No.1

<P><B>Summary</B></P><P>Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD‐dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD. SIRT3 mRNA and protein levels were significantly decreased in AD cerebral cortex, and Ac‐p53 K320 was significantly increased in AD mitochondria. SIRT3 prevented p53‐induced mitochondrial dysfunction and neuronal damage in a deacetylase activity‐dependent manner. Notably, mitochondrially targeted p53 (mito‐p53) directly reduced mitochondria DNA‐encoded ND2 and ND4 gene expression resulting in increased reactive oxygen species (ROS) and reduced mitochondrial oxygen consumption. ND2 and ND4 gene expressions were significantly decreased in patients with AD. p53‐ChIP analysis verified the presence of p53‐binding elements in the human mitochondrial genome and increased p53 occupancy of mitochondrial DNA in AD. SIRT3 overexpression restored the expression of ND2 and ND4 and improved mitochondrial oxygen consumption by repressing mito‐p53 activity. Our results indicate that SIRT3 dysfunction leads to p53‐mediated mitochondrial and neuronal damage in AD. Therapeutic modulation of SIRT3 activity may ameliorate mitochondrial pathology and neurodegeneration in AD.</P>

Expression of taurine transporter (TauT) is modulated by heat shock factor 1 (HSF1) in motor neurons of ALS.

Jung, Min-Kyung,Kim, Ki Yoon,Lee, Na-Young,Kang, Young-Sook,Hwang, Yu Jin,Kim, Yunha,Sung, Jung-Joon,McKee, Ann,Kowall, Neil,Lee, Junghee,Ryu, Hoon Humana Press 2013 Molecular neurobiology Vol.47 No.2

<P>Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive paralysis caused by the degeneration of motor neurons throughout the central nervous system. Mutations of the free radical scavenging enzyme Cu/Zn superoxide dismutase 1 (SOD1) are a cause of familial ALS. In the present study, we demonstrated an age-dependent increase in taurine transporter (TauT) immunoreactivity in spinal cord motor neurons of ALS transgenic mice (mutant SOD1 (G93A)) and a similar increase in TauT in spinal motor neurons of patients with ALS. Chromatin immunoprecipitation analysis verified that heat shock factor 1 (HSF1) preferentially occupies the HSF1 binding element in the promoter of TauT under oxidative stress conditions. Knockdown of HSF1 by small interfering RNA reduced the transcriptional activity of TauT. Using [(3)H] taurine, we confirmed that an elevated expression of TauT directly contributes to increased taurine uptake in ALS motor neurons. In addition, we showed that taurine plays an antioxidant role and may prevent motor neuron loss due to oxidative stress in ALS. Our findings suggest that HSF1-induced TauT expression partially protects motor neurons by compensating for constitutive oxidative stress, which is thought to be a key mechanism contributing to the pathogenesis of ALS. Taken together, our results suggest that TauT is a novel pathological marker for stressed motor neurons in ALS and that modulation of TauT and taurine may slow neuronal degeneration in ALS.</P>

Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy

서정선,이승복,신종연,황유진,조혜선,유승근,김윤하,임성수,김윤경,황은미,김수현,김종현,현승재,윤지영,김지혜,김요나,Victor E Alvarez,Thor D Stein,이정희,김동진,김종일,Neil W Kowall,류훈,Ann C McKee 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer’s disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.