Acquiring a selective growth advantage by breaking the proliferation barrier established by gatekeeper genes is a centrally important event in tumor formation. Removal of the mammalian Hippo kinase Mst1 and Mst2 in hepatocytes leads to rapid hepatocellular carcinoma (HCC) formation, indicating that the Hippo signaling pathway is a critical gatekeeper that restrains abnormal growth in hepatocytes. By rigorous genetic approaches, we identified an interacting network of the Hippo, Wnt/${\beta}$-catenin and Notch signaling pathways that control organ size and HCC development. We found that in hepatocytes, the loss of Mst1/2 leads to the activation of Notch signaling, which forms a positive feedback loop with Yap/Taz (transcription factors controlled by Mst1/2). This positive feedback loop results in severe liver enlargement and rapid HCC formation. Blocking the Yap/Taz-Notch positive feedback loop by Notch inhibition in vivo significantly reduced the Yap/Taz activities, hepatocyte proliferation and tumor formation. Furthermore, we uncovered a surprising inhibitory role of Wnt/${\beta}$-catenin signaling to Yap/Taz activities, which are important in tumor initiation. Genetic removal of ${\beta}$-catenin in the liver of the Mst1/2 mutants significantly accelerates tumoriogenesis. Therefore, Wnt/${\beta}$-catenin signaling, known for its oncogenic property, exerts an unexpected function in restricting Yap/Taz and Notch activities in HCC initiation. The molecular interplay between the three signaling pathways identified in our study provides new insights in developing novel therapeutic strategies to treat liver tumors.
Two experiments were conducted to standardize in ovo injection of amino acids (AA) and to evaluate the effect of in ovo injection of limiting AA(s) on pre and post hatch growth performance, immune response and development of digestive organs. Combinations of essential and non-essential amino acids (Lys+Arg, Lys+Met+Cys, Thr+Gly+Ser, Ile+Leu+Val and Gly+Pro) were injected into 50 eggs in each treatment group at 14 d of embryonic age. Standardization of injection site, needle length and embryonic age revealed that when AA were injected in to the broad end of the egg with a 11 mm needle and at the narrow end with a 24 mm needle both at the 7$^{th}$ and 14$^{th}$ d of incubation there was poor hatchability. However, better hatchability was recorded when the AA were injected in the narrow end of the egg with a 11 mm needle and in the broad end with a 24 mm needle on the 14$^{th}$ d of incubation. The chick to egg weight ratio was higher (p<0.018) when AA were injected on the 14$^{th}$ d of incubation. When a combination of amino acids were injected a 63.6 or 63.2 g difference in body weight of bird at 21 d was recorded between uninjected control and Ile+Leu+Val or Gly+Pro group, respectively. Higher feed intake (p<0.047) was recorded in the AA injected groups and feed conversion ratio (FCR) was numerically better in Gly+Pro, Lys+Met+Cys AA injected groups than in the uninjected control. Significantly higher immune response to cell mediated (p<0.033) and humoral (p<0.002) immunity was observed in in ovo amino acid injected birds, especially in Lys+Met+Cys, Thr+Gly+Ser or Ile+leu+Val groups. The digestive organ weights at 21 d did not differ between specific AA injected groups and the uninjected control. In ovo injected amino acids may act as immunomodulators and their role in gastrointestinal development needs further research.
Ko, Jung Min;Lee, Young Ah;Kim, Gi Beom;Park, Sung Sup;Song, Jung-Han
Journal of The Korean Society of Inherited Metabolic disease
/
v.12
no.1
/
pp.42-48
/
2012
Pompe disease is a rare lysosomal glycogen storage disorder caused by a total or partial deficiency of the acid ${\alpha}$-glucosidase (GAA) enzyme due to the GAA gene mutations. The classic infantile form of Pompe disease is a rapidly progressive multi-organ disease with hypotonia, generalized muscle weakness, and hypertrophic cardiomyopathy, usually leading to death in the first 2 years of life. Enzyme replacement therapy with recombinant human GAA has been shown to be effective and subsequently yielded promising results. Here, we present clinical and genetic characteristics of three Korean non-classic infantile Pompe patients, and the short term efficacy of enzyme replacement therapy. Considering that enzyme replacement therapy can change the natural course of infantile Pompe disease, early diagnosis and early initiation of treatment is critical to improving patient outcomes.
Skin is a major thermoregulatory organ in the body controlling homeothermy, a critical function for climate adaptation. We compared genes expressed between tropical- and temperate-adapted cattle to better understand genes involved in climate adaptation and hence thermoregulation. We profiled the skin of representative tropical and temperate cattle using RNA-seq. A total of 214,754,759 reads were generated and assembled into 72,993,478 reads and were mapped to unique regions in the bovine genome. Gene coverage of unique regions of the reference genome showed that of 24,616 genes, only 13,130 genes (53.34%) displayed more than one count per million reads for at least two libraries and were considered suitable for downstream analyses. Our results revealed that of 255 genes expressed differentially, 98 genes were upregulated in tropically-adapted White Fulani (WF; Bos indicus) and 157 genes were down regulated in WF compared to Angus, AG (Bos taurus). Fifteen pathways were identified from the differential gene sets through gene ontology and pathway analyses. These include the significantly enriched melanin metabolic process, proteinaceous extracellular matrix, inflammatory response, defense response, calcium ion binding and response to wounding. Quantitative PCR was used to validate six representative genes which are associated with skin thermoregulation and epithelia dysfunction (mean correlation 0.92; p < 0.001). Our results contribute to identifying genes and understanding molecular mechanisms of skin thermoregulation that may influence strategic genomic selection in cattle to withstand climate adaptation, microbial invasion and mechanical damage.
Gayen, Sanjib;Kombathula, Sri Harsha;Manna, Sumanta;Varshney, Sonal;Pareek, Puneet
Radiation Oncology Journal
/
v.38
no.2
/
pp.138-147
/
2020
Purpose: To evaluate the dosimetric variations in patients of head and neck cancer treated with definitive or adjuvant radiotherapy using optimized non-coplanar (ncVMAT) beams with coplanar (cVMAT) beams using volumetric arc therapy. Materials and Methods: Twenty-two patients of head and neck cancer that had received radiotherapy using VMAT in our department were retrospectively analyzed. Each of the patients was planned using coplanar and non-coplanar orientations using an optimized couch angle and fluences. We analyzed the Conformity Index (CIRTOG), Dose Homogeneity Index (DHI), Heterogeneity Index (HIRTOG), low dose volume, target and organs-at-risk coverage in both the plans without changing planning optimization parameters. Results: The prescription dose ranged from 60 Gy to 70 Gy. Using ncVMAT, CIRTOG, DHI and HIRTOG, and tumor coverage (ID95%) had improved, low dose spillage volume in the body V5Gy was increased and V10Gy was reduced. Integral dose and intensity-modulated radiation therapy factor had increased in ncVMAT. In the case of non-coplanar beam arrangements, maximum dose (Dmax) of right and left humeral head were reduced significantly whereas apex of the right and left lung mean dose were increased. Conclusion: The use of ncVMAT produced better target coverage and sparing of the shoulder and soft tissue of the neck as well as the critical organ compared with the cVMAT in patients of head and neck malignancy.
Journal of The Korean Society of Clinical Toxicology
/
v.19
no.2
/
pp.93-99
/
2021
Purpose: Nutritional status and support in critically ill patients are important factors in determining patient recovery and prognosis. The aim of this study was to analyze the early nutritional status and the methods of nutritional support in critically ill patients with acute poisoning and to evaluate the effect of nutritional status on prognosis. Methods: A retrospective study was conducted in tertiary care teaching hospital from January 2018 to December 2020. in an emergency department of university hospital, 220 patients who were stayed more than 2 days of poisoning in intensive care unit were enrolled. Results: 155 (70.5%) of patients with acute poisoning had low-risk in nutritional risk screening (NRS). Patients with malignancy had higher NRS (low risk 5.2%, moderate risk 18.5%, high risk 13.2%, p=0.024). Patients of 91.4% supplied nutrition via oral route or enteral route. Parenteral route for starting method of nutritional support were higher in patients with acute poisoning of herbicide or pesticide (medicine 3.2%, herbicide 13.8%, pesticide 22.2%, p=0.000). In multivariate logistic regression analysis, herbicide or pesticide intoxication, higher risk in NRS and sequential organ failure assessment over 4.5 were affecting factor on poor recovery at discharge. Conclusion: NRS in patients intoxicated with herbicide or pesticide were higher than that in patients intoxicated with medicine intoxication. Enteral nutrition in patients intoxicated with herbicide or pesticide was less common. Initial NRS was correlated with recovery at discharge in patient with intoxication. It is expected to be helpful in finding patients with high-risk nutritional status in acute poisoning patients and establishing a treatment plan that can actively implement nutritional support.
Journal of Physiology & Pathology in Korean Medicine
/
v.33
no.4
/
pp.191-197
/
2019
This study aims to evaluate the effects of the root bark of Morus alba (RMA) on the regulation of the Hippo-YAP pathway. Hippo-YAP signaling is a critical regulator in controlling organ size and tissue homeostasis. Hippo, the serine/threonine kinase phosphorylate the LATS. Phosphorylated LATS then phosphorylates and inactivates the YAP and TAZ, which are two closely related transcriptional co-activator. Here we report RMA activates the Hippo signaling, thereby inhibits the YAP/TAZ activity. First, we examine the cytotoxic effects of RMA by MTT assay. RMA was cytotoxic at concentrations higher than $50{\mu}g/ml$ in HEK293A cells. The reporter gene assay was performed to measure the activity of TEAD, a key transcription factor that controls cell growth and proliferation. RMA significantly suppressed the luciferase activity. By phos-taq gel shift assay, and western blotting, we showed that RMA enhanced the phosphorylation of YAP in wild type cells, but not in LATS1/2 knock out cells, which means RMA activates classical Hippo pathway. RMA induced the cytoplasmic sequestration of YAP. RMA also suppressed the mRNA expression of CTGF and CYR61; the two major YAP dependent genes. Taken together, RMA is considered to be a good candidate for proliferative disease such as cancer, by facilitating cell death through activating the Hippo signaling pathway.
Dhillan, Rishi;Bhalla, Alok;Kumar Jha, Sushil;Singh, Hakam;Arora, Aman
Journal of Trauma and Injury
/
v.32
no.2
/
pp.93-100
/
2019
Purpose: Penetrating vascular trauma though less common poses a challenge to all Surgeons. This study was designed to analyse the profile, management modalities of vascular trauma and the outcomes thereof at a Trauma Care Centre in a Tertiary care setting in hostile environment in India. Methods: A prospective review of all patients with arterial and venous injuries being transferred to the Trauma Center at out Tertiary Care Center between June 2015 and May 2018 was done. Demographics, admission data, treatment, and complications were reviewed. Results: There were a total of 46 patients with 65 vascular injuries, 39 arterial injuries and 26 venous injuries. The age range was 21 to 47 years. Nineteen patients had both arterial and venous injuries. A total of 42 cases presented within 12 hours of injury and complete arterial transections were found in 33 cases (80.49%). There were three mortalities (6.52%) and three amputations (8.33%). The overall limb salvage rate was 91.67% with popliteal artery being the commonest injured artery. Poor prognosticators for limb salvage were increasing time to present to the trauma centre, hypovolemic shock, multi-organ trauma and associated venous injuries. Conclusions: Penetrating missile trauma leading to vascular injuries has not been widely reported. Attempting limb salvage even in cases with delayed presentation should be weighed with the threat to life before revascularisation and should preferably be done at a centre with vascular expertise. A team approach with vascular, orthopaedic, general surgeons, and critical care anaesthesiologists all aboard improve the outcomes manifold. Use of tourniquets and early fasciotomies have been emphasized as is the use of native veins as the bypass conduit. This is probably the largest study on penetrating Vascular trauma in anti-terrorism ops from the Indian subcontinent. It highlights the significance of prompt recognition and availability of vascular expertise in optimally managing cases of vascular trauma.
Several factors, including genetic and environmental insults, impede protein folding and secretion in the endoplasmic reticulum (ER). Accumulation of unfolded or mis-folded protein in the ER manifests as ER stress. To cope with this morbid condition of the ER, recent data has suggested that the intracellular event of an unfolded protein response plays a critical role in managing the secretory load and maintaining proteostasis in the ER. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone and hydrophilic bile acid that is known to inhibit apoptosis by attenuating ER stress. Numerous studies have revealed that TUDCA affects hepatic diseases, obesity, and inflammatory illnesses. Recently, molecular regulation of ER stress in tooth development, especially during the secretory stage, has been studied. Therefore, in this study, we examined the developmental role of ER stress regulation in tooth morphogenesis using in vitro organ cultivation methods with a chemical chaperone treatment, TUDCA. Altered cellular events including proliferation, apoptosis, and dentinogenesis were examined using immunostaining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, altered localization patterns of the formation of hard tissue matrices related to molecules, including amelogenin and nestin, were examined to assess their morphological changes. Based on our findings, modulating the role of the chemical chaperone TUDCA in tooth morphogenesis, especially through the modulation of cellular proliferation and apoptosis, could be applied as a supporting data for tooth regeneration for future studies.
African swine fever (ASF) is a highly contagious disease of domestic pigs and wild boars (WBs). Without a vaccine, early antibody and antigen detection and rapid diagnosis are crucial for the effective prevention of the disease and the employment of control measures. In Sardinia, where 3 different suid populations coexisted closely for a long time, the disease persists since 1978. The recent ASF eradication plan involves more stringent measures to combat free-ranging pigs and any kind of illegality in the pig industry. However, critical issues such as the low level of hunter cooperation with veterinary services and the time required for ASF detection in the WBs killed during the hunting season still remain. Considering the need to deliver true ASF negative carcasses as early as possible, this study focuses on the evaluation and validation of a duplex pen-side test that simultaneously detects antibodies and antigens specific to ASF virus, to improve molecular diagnosis under field conditions. The main goal was to establish the specificity of the two pen-side tests performed simultaneously and to determine their ability to detect the true ASF negative carcasses among the hunted WBs. Blood and organ samples of the WBs hunted during the 2018/2019 hunting seasons were obtained. A total of 160 animals were tested using the pen-side kit test; samples were collected for virological and serological analyses. A specificity of 98% was observed considering the official laboratory tests as gold standards. The new diagnostic techniques could facilitate faster and cost-effective control of the disease.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.