673 research outputs found
Epidemiology and burden of soil-transmitted helminth infections among school-aged Bulang children in Yunnan province, People's Republic of China
No full textBackground: The three most common soil-transmitted helminths are Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), and Ancylostoma duodenale and Necator americanus (hookworms). Collectively, they infect around 1 billion people and put approximately 5 billion people at risk of infection worldwide. Strongyloides stercoralis is a less common soil-transmitted helminth than the species mentioned above, but still significant from a public health perspective. The global prevalence of S. stercoralis is estimated to be 30-100 million. Populations most affected by these parasitic worms are often impoverished, living on less than US$ 2 per day, and have poor sanitation facilities and hygiene habits. Despite the low prevalence levels of soil-transmitted helminth infections observed on a national level in the People’s Republic of China (P.R. China), hotspots of these infections, particularly within ethnic minority groups residing in rural areas, still exist.
Single-species infections with the common soil-transmitted helminths can cause symptoms ranging from abdominal pain to anaemia, and impaired development of cognitive abilities. For S. stercoralis infections, symptoms such as severe abdominal pain and blood in the stool have been reported. Due to the chronic and subtle nature of most morbidities commonly associated with soil-transmitted helminthiasis, it is difficult to assess the true burden due to these infections.
Objectives: The goal guiding this Ph.D. project was to deepen the understanding of the epidemiology and burden of soil-transmitted helminthiasis among school-aged children from the Bulang ethnic minority group in P.R. China. The following objectives were pursued: (i) to evaluate the feasibility of deploying different tools for the assessment of physical fitness in soil-transmitted helminth-endemic settings; (ii) to monitor changes in physical fitness, strength and anthropometric measurements over a six-month period among treated children and their untreated peers; (iii) to predict and visualize the change in physical fitness of school-aged children due to soil-transmitted helminth infections over a 1-month period across P.R. China; (iv) to assess the efficacy of triple-dose albendazole and study soil-transmitted helminth re-infection patterns after deworming; and (v) to estimate the odds of re-infection with soil-transmitted helminths for different natural nutritional statuses and types of nutritional supplementation.
Methods: For the field studies, parasitological examination of stool samples was performed. The Kato-Katz technique was used to identify the eggs of A. lumbricoides, hookworm, T. trichiura and other helminths, while the Baermann technique was used to identify the larvae of S. stercoralis. In addition, each stool sample was visually inspected for Taenia spp. proglottids. Physical fitness was estimated with the 20-m shuttle run test and physical strength was assessed with the grip strength and standing broad jump tests. Anthropometric measurements, including body height and weight and sum of skinfolds, and haemoglobin level were also recorded. Physical fitness and strength scores, anthropometric measurements, and haemoglobin level were expressed as means, and compared among children of distinct soil-transmitted helminth infection status and intensity. For the prediction and visualization exercise, the change in physical fitness over 1 month across P.R. China was predicted over a smooth surface of soil-transmitted helminth risk. Maps, with lower and upper boundaries of the predicted values as well as population-adjusted estimates, were further created. Finally, for the systematic review, the odds of re-infection with soil-transmitted helminths for different natural nutritional statuses and types of nutritional supplementation were estimated and qualitative content analysis was conducted for all studies included in the review.
Results: In a cross-sectional survey, the maximum aerobic capacity in 1 min of exhaustive exercise (VO2 max estimate) of T. trichiura-infected children was 1.9 ml kg-1 min-1 lower than that of their non-infected counterparts (P=0.01). Until exhaustion, T. trichiura-infected children had completed six 20-m laps less (P<0.01). No significant association between anthropometric indicators and infection with any soil-transmitted helminth species could be established.
In a randomised controlled trial, which investigated the effects of triple-dose albendazole on physical fitness of school-aged children, baseline prevalences of T. trichiura, A. lumbricoides, hookworm, and S. stercoralis were 94.5%, 93.3%, 61.3%, and 3.1% respectively, with more than half harboring triple-species infections. During the course of the trial, rapid re-infection with A. lumbricoides was observed and low cure rate was achieved with T. trichiura infections. Children receiving triple-dose albendazole scored slightly higher values in physical fitness and strength scores, anthropometric measurements, and haemoglobin level than placebo recipients, but the difference lacked statistical significance. The increase in VO2 max estimate from baseline was 1.6 ml kg-1 min-1 (P=0.02) less and the increase in the number of 20-m laps completed from baseline was five 20-m laps (P=0.04) less for T. trichiura-infected children compared to their non-infected peers. In addition, children with low infection intensity of T. trichiura and hookworm had consistently more increase in the VO2 max estimate from baseline than their peers with high infection intensity of all soil-transmitted helminths (range: 1.9-2.1 ml kg-1 min-1; all P <0.05).
In the systematic review, multi-micronutrients seemed to have the clearest effect with regards to lowering re-infection rates and intensity of soil-transmitted helminths, whereas consumption of zinc or vitamin A alone might have a negative impact on these two outcomes measures. With regards to the natural nutrition status of the host, the general trend observed was that individuals with poor nutrition status suffered higher re-infection rates and intensities when compared to their well-nourished peers. Overall, only fifteen studies met our inclusion criteria and majority of them were of low quality.
Conclusions/significance: The negative associations observed between T. trichiura infections and physical fitness among school-aged Bulang children in Yunnan suggests that the current burden estimate of soil-transmitted helminth infections, in particular T. trichiura infections, might be underestimated and there are still subtle and hidden morbidities to be quantified. A paradigm shift is needed to further understand the burden of soil-transmitted helminth infections as the presence of co-infections and co-morbidities add layers of complexity to the task. Finally, the epidemiological findings on soil-transmitted helminthiasis from this thesis highlight that a national soil-transmitted helminth control programme is overdue and urgently needed as P.R. China further develops into a global powerhouse. With many of their rural communities starting to have their hands on the first rung of the development ladder, P.R. China seems to be in a good position to set a leading example on how to control and eliminate soil-transmitted helminthiasis, and possibly other neglected tropical diseases, for developing countries around the world
Influence of nutrition on infection and re-infection with soil-transmitted helminths : a systematic review
No full textBACKGROUND: The relationship between nutrition and soil-transmitted helminthiasis is complex and warrants further investigation. We conducted a systematic review examining the influence of nutrition on infection and re-infection with soil-transmitted helminths (i.e. Ascaris lumbricoides, hookworm, Trichuris trichiura and Strongyloides stercoralis) in humans. Emphasis was placed on the use of nutritional supplementation, alongside anthelminthic treatment, to prevent re-infection with soil-transmitted helminths. METHODS: We searched eight electronic databases from inception to 31 July 2013, with no restriction of language or type of publication. For studies that met our inclusion criteria, we extracted information on the soil-transmitted helminth species, nutritional supplementation and anthelminthic treatment. Outcomes were presented in forest plots and a summary of findings (SoF) table. An evidence profile (EP) was generated by rating the evidence quality of the identified studies according to the GRADE system. RESULTS: Fifteen studies met our inclusion criteria; eight randomised controlled trials and seven prospective cohort studies. Data on A. lumbricoides were available from all studies, whereas seven and six studies additionally contained data on T. trichiura and hookworm, respectively. None of the studies contained data on S. stercoralis. Positive effects of nutritional supplementation or the host's natural nutritional status on (re-)infection with soil-transmitted helminths were reported in 14 studies, while negative effects were documented in six studies. In terms of quality, a high, low and very low quality rating was assigned to the evidence from four, six and five studies, respectively. CONCLUSIONS: Our findings suggest that the current evidence-base is weak, precluding guidelines on nutrition management as a potential supplementary tool to preventive chemotherapy targeting soil-transmitted helminthiasis. Moreover, several epidemiological, immunological and methodological issues have been identified, and these should be considered when designing future studie
Enabling data sharing and utilization for African population health data using OHDSI tools with an OMOP-common data model
No full textThe COVID-19 pandemic has spurred the use of AI and DS innovations in data collection and aggregation. Extensive data on many aspects of the COVID-19 has been collected and used to optimize public health response to the pandemic and to manage the recovery of patients in Sub-Saharan Africa. However, there is no standard mechanism for collecting, documenting and disseminating COVID-19 related data or metadata, which makes the use and reuse a challenge. INSPIRE utilizes the Observational Medical Outcomes Partnership (OMOP) as the Common Data Model (CDM) implemented in the cloud as a Platform as a Service (PaaS) for COVID-19 data. The INSPIRE PaaS for COVID-19 data leverages the cloud gateway for both individual research organizations and for data networks. Individual research institutions may choose to use the PaaS to access the FAIR data management, data analysis and data sharing capabilities which come with the OMOP CDM. Network data hubs may be interested in harmonizing data across localities using the CDM conditioned by the data ownership and data sharing agreements available under OMOP's federated model. The INSPIRE platform for evaluation of COVID-19 Harmonized data (PEACH) harmonizes data from Kenya and Malawi. Data sharing platforms must remain trusted digital spaces that protect human rights and foster citizens' participation is vital in an era where information overload from the internet exists. The channel for sharing data between localities is included in the PaaS and is based on data sharing agreements provided by the data producer. This allows the data producers to retain control over how their data are used, which can be further protected through the use of the federated CDM. Federated regional OMOP-CDM are based on the PaaS instances and analysis workbenches in INSPIRE-PEACH with harmonized analysis powered by the AI technologies in OMOP. These AI technologies can be used to discover and evaluate pathways that COVID-19 cohorts take through public health interventions and treatments. By using both the data mapping and terminology mapping, we construct ETLs that populate the data and/or metadata elements of the CDM, making the hub both a central model and a distributed model
MAPK-Mediated YAP Activation Controls Mechanical-Tension-Induced Pulmonary Alveolar Regeneration
No full textSummaryThe pulmonary alveolar epithelium undergoes extensive regeneration in response to lung injuries, including lung resection. In recent years, our understanding of cell lineage relationships in the pulmonary alveolar epithelium has improved significantly. However, the molecular and cellular mechanisms that regulate pneumonectomy (PNX)-induced alveolar regeneration remain largely unknown. In this study, we demonstrate that mechanical-tension-induced YAP activation in alveolar stem cells plays a major role in promoting post-PNX alveolar regeneration. Our results indicate that JNK and p38 MAPK signaling is critical for mediating actin-cytoskeleton-remodeling-induced nuclear YAP expression in alveolar stem cells. Moreover, we show that Cdc42-controlled actin remodeling is required for the activation of JNK, p38, and YAP in post-PNX lungs. Our findings together establish that the Cdc42/F-actin/MAPK/YAP signaling cascade is essential for promoting alveolar regeneration in response to mechanical tension in the lung
Enigma proteins regulate YAP mechanotransduction
No full textHuman cells can sense mechanical stress acting upon integrin adhesions and respond by sending the YAP (also known as YAP1) and TAZ (also known as WWTR1) transcriptional co-activators to the nucleus to drive TEAD-dependent transcription of target genes. How integrin signaling activates YAP remains unclear. Here, we show that integrin-mediated mechanotransduction requires the Enigma and Enigma-like proteins (PDLIM7 and PDLIM5, respectively; denoted for the family of PDZ and LIM domain-containing proteins). YAP binds to PDLIM5 and PDLIM7 (hereafter PDLIM5/7) via its C-terminal PDZ-binding motif (PBM), which is essential for full nuclear localization and activity of YAP. Accordingly, silencing of PDLIM5/7 expression reduces YAP nuclear localization, tyrosine phosphorylation and transcriptional activity. The PDLIM5/7 proteins are recruited from the cytoplasm to integrin adhesions and F-actin stress fibers in response to force by binding directly to the key stress fiber component α-actinin. Thus, forces acting on integrins recruit Enigma family proteins to trigger YAP activation during mechanotransduction.This article has an associated First Person interview with the first author of the paper
Inhibition of YAP ameliorates renal fibrosis through FGF2 pathway
No full textThe Hippo pathway is an evolutionarily conserved kinase cascade that controls organ size by regulating cell proliferation, differentiation, migration, and apoptosis. Activation of the Hippo pathway leads to the phosphorylation of mammalian Ste20-like kinases 1/2 (MST1/2) and large tumor suppressor 1/2 (LAT1/2), the latter in turn inhibits the core effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) through phosphorylation and thus inhibiting their nuclear localization. On the other hand, inactivation of the Hippo pathway leads to YAP/TAZ activation through promoting YAP/TAZ dephosphorylation and nuclear retention. Once activated, YAP/TAZ interact with TEAD or other transcription factors to induce the expression of a wide range of their downstream genes. Recently, the protein level of YAP was reported to be higher in the kidney of diabetic mice and in renal proximal tubule epithelial cells in response to high glucose, indicating that YAP may play a role in the pathogenesis of diabetic kidney disease.In the present study, we observed that the expression of both YAP and fibroblast growth factor 2 (FGF2) is higher in kidneys of diabetic db/db mice. Oral gavage of atorvastatin (10 mg/kg/daily), a lipid-lowering drug with newly identified YAP inhibitory property, alleviates albuminuria, glomerular hypertrophy, and renal fibrosis in db/db mice, accompanied by reduced renal expression of YAP and FGF2. To investigate whether hyperglycemia in diabetic conditions promotes YAP activation and FGF2 over-expression in kidney cells, we treated human proximal renal tubular epithelial cells (HK2) with 30 mM glucose for 48 hours and found that high glucose increased the mRNA level of YAP target genes (ANKRD1, CTGF, and CYR61) and FGF2. To explore if YAP/TAZ control the FGF2 expression, we transfected HK2 cells with plasmids expressing YAP/TAZ and showed that both expression and secretion of FGF2 were induced by YAP/TAZ over-expression. Oppositely, knockdown of YAP/TAZ decreased the expression of FGF2. The FGF2-promoter reporter gene assay further confirmed that YAP/TAZ promote the FGF2 expression at the transcriptional level. To investigate the effect of YAP activation in renal fibrosis, we constructed the Ksp-Cre transgenic MST1/MST2 double knockout (dKO) mice to achieve kidney-specific YAP activation. The results revealed that the expression of FGF2 is increased in dKO mice accompanied by renal fibrosis development at 8 weeks of age. While tubular-specific MST1/MST2/YAP triple knockout (tKO) mice were partly rescued from renal fibrosis in dKO mice with decreased expression of FGF2. To further clarify if FGF2 mediates YAP/TAZ-induced renal fibrosis, we injected the renal pelvis of dKO mice with the adeno-associated virus carrying CRISPR/Cas9-mediated FGF2 knockdown sequences. As the results showed, one month after virus injection, the FGF2 expression was significantly decreased and the renal fibrosis was ameliorated in the mouse kidneys. Taken together, the present results suggest that YAP activation promotes renal fibrosis through inducing the FGF2 expression and inhibition of YAP ameliorate renal fibrosis partly through decreasing the expression of FGF2.Hippo信號通路是壹條進化上非常保守的信號通路，通過調節細胞增殖，分化，遷移和雕亡來控制器官的大小。 Hippo信號通路的激活導致哺乳動物MST1 / 2激酶和腫瘤抑制因子LAT1 / 2的磷酸化，最終抑制了轉錄共激活因子 YAP 和 TAZ，通過磷酸化作用抑制其入核。另壹方面，Hippo信號通路的失活通過促進YAP / TAZ去磷酸化和入核而導致YAP / TAZ活化。激活後，YAP / TAZ與TEAD或其他轉錄因子相互作用，並誘導其下遊基因的廣泛表達。研究發現，糖尿病小鼠的腎臟和高糖刺激的人近端腎小管上皮細胞中YAP激活，這表明YAP可能參與糖尿病腎病的發病機理。在本研究中，我們發現糖尿病小鼠（db/db）腎臟中的YAP和FGF2表達升高。應用壹種具有YAP抑制特性的降脂藥物阿托伐他汀灌胃（10 mg / kg / 每日），可抑制YAP和FGF2表達，並減輕db/db小鼠的蛋白尿，腎小球肥大和腎纖維化。為了研究糖尿病患者中的高血糖是否促進YAP激活和FGF2的表達，我們用30 mM葡萄糖處理人近端腎小管上皮細胞（HK2）48小時，發現高糖會增加YAP靶基因（ANKRD1，CTGF和CYR61）和FGF2的表達。為了探討YAP / TAZ是否調控FGF2的表達，我們在HK2細胞中過表達YAP / TAZ，發現 YAP / TAZ過表達誘導了FGF2的表達和分泌。相反，YAP / TAZ 敲低降低了FGF2的表達。 FGF2-啟動子報告基因檢測進壹步證實了YAP/TAZ 在轉錄水平調節FGF2表達。為了研究YAP激活在腎纖維化中的作用，我們構建了腎小管特異性MST1 / MST2雙敲除（dKO）小鼠，以實現腎小管特異性YAP激活。實驗結果表明，在8周齡的dKO小鼠中，伴隨著腎纖維化的發展，FGF2的表達增加。腎小管特異性MST1 / MST2 / YAP三重敲除（tKO）小鼠，FGF2的表達下調，腎纖維化有所緩解。為了進壹步闡明FGF2是否參與YAP / TAZ誘導的腎纖維化，我們用帶有CRISPR / Cas9介導的FGF2敲除序列的腺相關病毒對dKO小鼠進行腎盂註射。結果表明，註射後1個月，FGF2表達顯著降低，腎纖維化得到改善。綜上所述，這些結果表明YAP活化通過誘導FGF2表達促進腎纖維化，阿托伐他汀對YAP的抑制可以部分通過降低FGF2的表達改善腎纖維化。Wang, Yu."December 2020."Ph.D. Chinese University of Hong Kong 2021.Includes bibliographical references (leaves 113-121).Abstracts also in Chinese.Title from PDF title page (viewed on September 13, 2022)
Enigma proteins regulate YAP mechanotransduction
No full textHuman cells can sense mechanical stress acting upon integrin adhesions and respond by sending the YAP (also known as YAP1) and TAZ (also known as WWTR1) transcriptional co-activators to the nucleus to drive TEAD-dependent transcription of target genes. How integrin signaling activates YAP remains unclear. Here, we show that integrin-mediated mechanotransduction requires the Enigma and Enigma-like proteins (PDLIM7 and PDLIM5, respectively; denoted for the family of PDZ and LIM domain-containing proteins). YAP binds to PDLIM5 and PDLIM7 (hereafter PDLIM5/7) via its C-terminal PDZ-binding motif (PBM), which is essential for full nuclear localization and activity of YAP. Accordingly, silencing of PDLIM5/7 expression reduces YAP nuclear localization, tyrosine phosphorylation and transcriptional activity. The PDLIM5/7 proteins are recruited from the cytoplasm to integrin adhesions and F-actin stress fibers in response to force by binding directly to the key stress fiber component α-actinin. Thus, forces acting on integrins recruit Enigma family proteins to trigger YAP activation during mechanotransduction.This article has an associated First Person interview with the first author of the paper
Mathematical Modeling of the YAP/TAZ Pathways
No full textabstract: YAP/TAZ is the key effector in the Hippo pathway, but it is also involved in many other regulatory pathways to control tissue and organ size. To better understand its regulation and effects in tumorigenesis and degeneration, a preliminary feedback network was created with the species YAP/TAZ, phosphorylated YAP/TAZ, LATS, miR-130a, VGLL4, and β-catenin. From this network a set of ordinary differential equations were written and analyzed for parameter effects. A model showing the healthy, tumorigenic, and degenerative states was created and preliminary parameter analysis identified the effects of parameter modifications on the overall levels of YAP/TAZ. Further analysis is required and connections with the underlying biology should continue to be pursued to better understand how parameter modifications could improve disease treatments
The metabolic role of YAP in liver regeneration
No full textPh.D.The Hippo signaling pathway has attracted broad interest in the liver research, particularly regarding its role in liver size control and tumorigenesis. However, the implication of the Hippo signaling in liver regeneration and drug-induced liver injury (DILI) are understudied. Therefore, the first part of this thesis aims to investigate the role of YAP, the downstream effector of the Hippo pathway, in the metabolic adaptations during early liver regeneration. The second part of the thesis is to explore the contribution of YAP to acetaminophen (APAP)-induced hepatotoxicity.We thereby generated hepatocyte-specific Yap knockout ( Yap KO) mice by tail vein injection of AAV-TBG-Cre to floxed Yap mice to examine the effect of YAP in mature hepatocytes. In the first series of experiments, we used partial hepatectomy (PH) as the surgical model to study liver regeneration. We found that YAP’s target gene Ctgf and Ankrd1 were robustly elevated during the first 4-8 hours following PH, prior to the initiation of hepatocyte proliferation, indicating that YAP activation is an early liver regenerative response. We further demonstrated that YAP deficiency exacerbated the regenerative-associated transient liver steatosis by increased adipose tissue lipolysis and enhanced fatty acid uptake and esterification. Such lipid overload was in part due to the aggravated hepatic insufficiency, as reflected by the concomitantly increased fatty acid oxidation, reduced intracellular acetyl-CoA level, and suppressed lipogenesis. Such impaired energy metabolism might in part account for the compromised liver regeneration in Yap knockout mouse.In the second set of experiments, we showed for the first time that YAP regulates the expression of cytochrome P450 (CYP) enzymes CYP2E1 and CYP1A2, which catalyze the bioactivation of APAP to form the hepatotoxic metabolite NAPQI. In cultured primary mouse hepatocytes, YAP knockdown stabilized CYP2E1 and CYP1A2. Upon APAP (5 mM) treatment, YAP knockdown increased the transcription of CYP2E1 and CYP1A2. Consistently, hepatocyte-specific Yap knockout mouse liver showed the elevated expression of CYP2E1 and CYP1A2 at 15 min after being oral challenged with a toxic dose of APAP (500mg/kg body weight). This was accompanied by downregulated expression of genes involved in oxidative phosphorylation and a reduced expression of important mitochondrial fusion protein OPA1, thus pointing to an altered mitochondrial function. Consequently, these alterations led to an exacerbated centrilobular necrosis in Yap KO mouse liver at 24 hours after APAP overdose.In summary, the present study demonstrates that YAP actively participates in the partition of energy prior to the hepatocyte repopulation during liver regeneration. In addition, we also reveal a previously unreported link between YAP and hepatic drugmetabolism via modulating the CYP enzymes. This study shed light on the metabolic role of YAP in liver regeneration, indicating that fine-tuned modulation of YAP activity could be a possible strategy to promote tissue repair after liver resection or acute liver injury.Hippo 信號通路在肝臟研究領域中得到了廣泛的關注，特別是關於其在控制肝臟器官大小及腫瘤形成中的作用。然而，Hippo 信號通路在肝再生和藥物性肝損傷 (DILI) 中的作用的相關研究卻較少被涉及。因此，本論文的第一部分旨在研究Hippo 信號通路的下游效應物YAP 在肝再生過程的中早期代謝適應中所扮演的角色。本論文的第二部分旨在探討YAP 在對乙酰氨基酚 (APAP) 產生肝毒性過程中所起的作用。我們通過對floxed Yap 小鼠進行尾靜脈注射AAV-TBG-Cre 腺相關病毒從而建立肝細胞特異性Yap 基因敲除 (Yap KO) 小鼠，以研究YAP 在成熟肝細胞中的作用。在第一部分的論文中，我們使用部分肝切除術 (PH) 作為研究肝臟再生的模型。我們發現，在肝部分切除後的4-8小時內YAP的靶基因Ctgf和Ankrd1的轉錄被激活，在肝細胞增殖前期表達量升高，這表明YAP 的活化是作為肝再生的一個早期反應。我們進一步證明，Yap 基因敲除小鼠通過增加白色脂肪組織的脂解作用和增強脂肪酸的攝取和脂化作用，從而加劇了肝再生所伴隨的短暫性肝脂肪變性。這種脂質負荷的現像是部分由於加劇的肝功能不全所導致的，表現為伴有脂肪酸氧化增加，細胞內乙酰輔酶A水平降低，以及脂肪酸合成受到抑制。這種能量代謝受損的狀態可能是Yap 基因敲除小鼠出現肝再生受損表型的部分成因。在第二部分的論文中，我們首次證明了YAP 能夠調節細胞色素P450 酶2E1(CYP2E1)和1A2 (CYP1A2)的表達。這些酶參與催化對乙酰氨基酚的活化反應從而產生具有肝細胞毒性的代謝產物NAPQI。在原代培養的小鼠肝細胞中，YAP 敲低可以穩定CYP2E1 和CYP1A2 的蛋白表達。經對乙酰氨基酚 (5 mM)處理後，YAP 敲低的肝細胞顯示出CYP2E1 和CYP1A2 轉錄的增加。這與用對乙酰氨基酚 (500 mg/kg body weight) 誘導小鼠肝損傷動物模型的結果一致。肝細胞特異性Yap 基因敲除小鼠的肝臟在處理15 分鐘後顯示出升高的CYP2E1和CYP1A2表達。同時伴有與氧化磷酸化通路相關基因的下調，以及參與線粒體融合的關鍵蛋白OPA1 的表達降低，這些結果表明線粒體功能發生了改變。因此，這些因素導致在過量對乙酰氨基酚處理24 小時後在Yap 基因敲除小鼠的肝臟中發現了更加嚴重的小葉中心壞死的現象。綜上所述，實驗結果表明YAP 在肝再生過程中參與了肝細胞增殖前的能量分配。此外，我們還首次揭示了YAP 通過調節細胞色素酶的表達從而與肝臟藥物代謝過程之間產生聯繫。這項研究揭示了YAP 在肝臟再生中代謝方面的作用，表明對YAP 活性的微調可能是促進肝切除或急性肝損傷後組織修復的一種可行策略。Wang, Yifan.Thesis Ph.D. Chinese University of Hong Kong 2020.Includes bibliographical references (leaves 100-113).Abstracts also in Chinese.Title from PDF title page (viewed on February 10, 2022)
1H, 13C, 15N resonance assignment of human YAP 50–171 fragment
No full textYes associated protein (YAP) is an intrinsically disordered protein that plays a major role in the Hippo pathway, regulating organ size, cell proliferation, apoptosis, and is associated with cancer development. Therefore, the binding between YAP and TEAD is an interesting target for cancer therapy. The TEAD binding domain of YAP was mapped to protein residues 50–171. To obtain further structural insights into this 12 kDa segment of YAP, we report a backbone and a partial sidechain assignment of recombinant YAP 50–171.© The Author(s) 201
- …
