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Canaud, Guillaume, Craig R. Brooks, Seiji Kishi, Kensei Taguchi, Kenji Nishimura, Sato Magassa, Adam Scott, et al. "Cyclin G1 and TASCC regulate kidney epithelial cell G2-M arrest and fibrotic maladaptive repair." Science Translational Medicine 11, no. 476 (January 23, 2019): eaav4754. http://dx.doi.org/10.1126/scitranslmed.aav4754.
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Fibrosis contributes to the progression of chronic kidney disease (CKD). Severe acute kidney injury can lead to CKD through proximal tubular cell (PTC) cycle arrest in the G2-M phase, with secretion of profibrotic factors. Here, we show that epithelial cells in the G2-M phase form target of rapamycin (TOR)–autophagy spatial coupling compartments (TASCCs), which promote profibrotic secretion similar to the senescence-associated secretory phenotype. Cyclin G1 (CG1), an atypical cyclin, promoted G2-M arrest in PTCs and up-regulated TASCC formation. PTC TASCC formation was also present in humans with CKD. Prevention of TASCC formation in cultured PTCs blocked secretion of profibrotic factors. PTC-specific knockout of a key TASCC component reduced the rate of kidney fibrosis progression in mice with CKD. CG1 induction and TASCC formation also occur in liver fibrosis. Deletion of CG1 reduced G2-M phase cells and TASCC formation in vivo. This study provides mechanistic evidence supporting how profibrotic G2-M arrest is induced in kidney injury and how G2-M–arrested PTCs promote fibrosis, identifying new therapeutic targets to mitigate kidney fibrosis.
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Marotta, Gianluca, Paola Sansoni, Franco Francini, David Jafrancesco, Maurizio De Lucia, and Daniela Fontani. "Structured Light Profilometry on m-PTC." Energies 13, no. 21 (October 29, 2020): 5671. http://dx.doi.org/10.3390/en13215671.
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In concentrating solar systems, it is essential to study the optical losses of the collectors. A fundamental parameter is the intercept factor, namely, the fraction of sunrays reflected by the concentrator that reaches the receiver. Optical profilometry studies the relationship between the collector profile and the intercept factor, which influences the collection efficiency. Profilometric analyses were performed on a micro-parabolic trough collector (m-PTC), with reduced sizes and greater mirror curvature than a usual PTC. The proposed technique projects a luminous pattern (structured light) both on the collector with an opaque covering and on a flat reference plane. Measurement set-up and calibration technique were developed for m-PTC. A program coded in Python analyzed the images and reconstructs the mirror profile. The tilted reference plane was reconstructed using an original geometric model and a calibration procedure. The focal length of each parabolic section was calculated, providing information on surface defects in the mirror. An important parameter obtained was the displacement of the focus of the parabola with respect to the ideal position. Using this value, the intercept factor was estimated to be 0.89. The proposed technique was validated by comparing the results with an independent profilometric study applied to the same m-PTC.
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Lee, Olivia W., Danielle M. Karyadi, Chip Stewart, Tetiana I. Bogdanova, Jieqiong Dai, Stephen W. Hartley, Sara J. Schonfeld, et al. "Abstract 980: Genomic characterization of lymph node metastases in papillary thyroid carcinoma following the Chernobyl accident reveals an expression profile specific to metastatic process." Cancer Research 82, no. 12_Supplement (June 15, 2022): 980. http://dx.doi.org/10.1158/1538-7445.am2022-980.
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Abstract Following the Chernobyl nuclear power plant explosion in Ukraine in 1986, increased childhood exposure to radioactive iodine (131I), which occurred primarily through contaminated food sources, has been consistently associated with increased risk of developing papillary thyroid carcinoma (PTC). Increased frequency of cervical lymph node metastases (LNM) is well recognized in pediatric PTC, including pediatric cases following the Chernobyl accident. We recently leveraged the collection of fresh-frozen tumor tissues from the Chernobyl Tissue Bank to conduct a genomic landscape analysis of 440 cases of PTC that provided new insights into radiation-related molecular characteristics of PTC occurring after the accident (Morton et al., Science 2021). Here, we extend that study to conduct a genomic landscape analysis of LNMs for a subset of 48 PTC cases to investigate the specific genomic alterations occurring in LNM. The analysis set comprised 144 samples, including fresh-frozen treatment-naïve primary and LNM PTC tumor samples as well as matched normal tissue or blood. Overall, the mutational load was highly concordant between primary and metastatic PTC. On average, 50% of somatic single nucleotide variants and 97% structural variants were shared between primary and metastatic PTCs. In contrast, the burden of somatic copy number alterations (SCNA) between primary tumor and LNM pairs was less concordant, particularly for copy number gains, whereas most of the copy number loss was found to be shared between matched pairs. PTC is usually driven by one driver mutation, most often involving the mitogen-activated protein kinase (MAPK) pathway. All driver mutations were shared between primary and metastatic PTC and were clonal; thus, no additional driver mutations were detected in metastatic PTC. Notably, however, the matched pairs in this study disproportionately had fusion drivers (77%), whereas only 23% of the drivers were BRAF V600E and none were RAS mutations. Transcriptome analysis revealed differentially expressed genes (DEGs) in metastatic PTC compared to primary PTC; three-quarters of the DEGs were overexpressed in metastatic PTC. Half of the LNM overexpressed DEGs were members of the HOXC family, which has been linked with epithelial-mesenchymal transition in cancer progression. There was also reduced expression in LNM for the DLX family, which relates to TGF-beta signaling. Our findings did not reveal a relationship between radiation dose and expression profiles in the LNM, comparable to our findings for the primary PTCs. We still observe that the efficiency of the radiation-induced PTC is paramount and subsequent events are directly related to the drivers in the MAPK pathway. For the cervical LNMs, we observed expression profiles not observed in the primary PTC that could give new insights into PTC local metastases. Citation Format: Olivia W. Lee, Danielle M. Karyadi, Chip Stewart, Tetiana I. Bogdanova, Jieqiong Dai, Stephen W. Hartley, Sara J. Schonfeld, Vidushi Kapoor, Marko Krznaric, Meredith Yeager, Amy Hutchinson, Belynda D. Hicks, Casey L. Dagnall, Julie M. Gastier-Foster, Jay Bowen, Mitchell J. Machiela, Elizabeth K. Cahoon, Kiyohiko Mabuchi, Vladimir Drozdovitch, Sergii Masiuk, Mykola Chepurny, Liudmyla Y. Zurnadzhy, Amy Berrington de González, Gad Getz, Gerry A. Thomas, Mykola D. Tronko, Lindsay M. Morton, Stephen J. Chanock. Genomic characterization of lymph node metastases in papillary thyroid carcinoma following the Chernobyl accident reveals an expression profile specific to metastatic process [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 980.
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Pan, Yujia, Weikang Yun, Bingshuai Shi, Rongjun Cui, Chi Liu, Zhong Ding, Jialin Fan, et al. "Downregulation of miR-146b-5p via iodine involvement repressed papillary thyroid carcinoma cell proliferation." Journal of Molecular Endocrinology 65, no. 2 (August 2020): 1–10. http://dx.doi.org/10.1530/jme-19-0198.
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miR-146b-5p is overexpressed in papillary thyroid carcinoma (PTC) and is thought to be a related diagnostic marker. Previous studies have indicated the effects of iodine on oncogenic activation. However, the effect of iodine on the proliferation of PTC cells and the associated underlying mechanisms remain unclear. We found that miR-146b-5p was downregulated and smad4 was upregulated in patients exposed to high iodine concentration by in situ hybridisation (ISH) and immunohistochemical (IHC). NaI (10−3 M) treatment downregulated miR-146b-5p and upregulated Smad4 in PTC cell lines. Luciferase assay was used to confirm that Smad4 is a target of miR-146b-5p. Furthermore, MTT assay and cell cycle analysis indicated that 10−3 M NaI suppressed cell proliferation and caused G0/G1 phase arrest. Real-time PCR and Western blotting demonstrated that 10−3 M NaI increased p21, p27, and p57 levels and reduced cyclin D1 levels in PTC cells. Our findings suggest that 10−3 M NaI increases Smad4 levels through repression of miR-146b-5p expression, curbing the proliferation in PTC.
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Teo, Aik-Chuan, Garry Wei-Han Tan, Keng-Boon Ooi, Teck-Soon Hew, and King-Tak Yew. "The effects of convenience and speed in m-payment." Industrial Management & Data Systems 115, no. 2 (March 9, 2015): 311–31. http://dx.doi.org/10.1108/imds-08-2014-0231.
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Purpose – The purpose of this paper is to uncover the effects of perceived transaction convenience (PTC) and perceived transaction speed (PTS) on unified theory of acceptance and use of technology (UTAUT) in the context of m-payment. Design/methodology/approach – A predictive analysis approach was used to examine the PTC and PTS using a two-stage partial least square (PLS) and neural network (NN) analyses. Findings – The findings reveal that only effort expectancy (EE) and facilitating conditions (FC) were discovered to significantly influence BI. More importantly, PTC was found to have positive significant relationship with EE and performance expectancy (PE). Moreover, PTS also supported the positive relationship with BI and EE. Practical implications – The findings of the study provided further insights to mobile payment service providers, online banking industry players, and all decision makers and stakeholders involved. Originality/value – Despite of many attempts devoted to understand m-payment adoption, the effects of PTC and PTS on m-payment are not well understood.
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Pinto, António E., Giovani L. Silva, Rui Henrique, Francisco D. Menezes, Manuel R. Teixeira, Valeriano Leite, and Branca M. Cavaco. "Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour." European Journal of Endocrinology 170, no. 2 (February 2014): 321–27. http://dx.doi.org/10.1530/eje-13-0865.
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ObjectiveFamilial non-medullary thyroid cancer has been proposed as an aggressive clinical entity. Our aim in this study is to investigate potential distinguishing features as well as the biological and clinical aggressiveness of familial vs sporadic papillary thyroid carcinoma (PTC). We assessed clinicopathological characteristics, outcome measures and DNA ploidy.DesignA matched-case comparative study.MethodsA series of patients with familial PTC (n=107) and two subgroups, one with three or more affected elements (n=32) and another including index cases only (n=61), were compared with patients with sporadic PTC (n=107), matched by age, gender, pTNM disease extension and approximate follow-up duration. Histological variant, extrathyroidal extension, vascular invasion, tumour multifocality and bilateral growth were evaluated. Ploidy pattern was analysed in available samples by DNA flow cytometry. The probabilities of disease-free survival (DFS) and overall survival (OS) were estimated according to the Kaplan–Meier (K–M) method.ResultsNo patient with familial PTC died of disease during follow-up (median, 72 months), contrarily to five patients (4.7%) (P=0.06) with sporadic PTC (median, 90 months). There was a significantly higher tumour multifocality in familial PTC (index cases subgroup) vs sporadic PTC (P=0.035), and a trend, in the familial PTC cohort with three or more affected elements, to show extrathyroidal extension (P=0.054) more frequently. No difference was observed in DNA ploidy status. The K–M analyses showed no significant differences between both entities in relation to DFS or OS.ConclusionApart from multifocality, familial PTC appears to have similar clinical/prognostic behaviour when compared with sporadic forms of the disease.
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Mizuno, Ju, Satoshi Mohri, Takeshi Yokoyama, Mikiya Otsuji, Hideko Arita, and Kazuo Hanaoka. "Temperature-dependent inotropic and lusitropic indices based on half-logistic time constants for four segmental phases in isovolumic left ventricular pressure–time curve in excised, cross-circulated canine heart." Canadian Journal of Physiology and Pharmacology 95, no. 2 (February 2017): 190–98. http://dx.doi.org/10.1139/cjpp-2015-0196.
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Varying temperature affects cardiac systolic and diastolic function and the left ventricular (LV) pressure–time curve (PTC) waveform that includes information about LV inotropism and lusitropism. Our proposed half-logistic (h-L) time constants obtained by fitting using h-L functions for four segmental phases (Phases I–IV) in the isovolumic LV PTC are more useful indices for estimating LV inotropism and lusitropism during contraction and relaxation periods than the mono-exponential (m-E) time constants at normal temperature. In this study, we investigated whether the superiority of the goodness of h-L fits remained even at hypothermia and hyperthermia. Phases I–IV in the isovolumic LV PTCs in eight excised, cross-circulated canine hearts at 33, 36, and 38 °C were analyzed using h-L and m-E functions and the least-squares method. The h-L and m-E time constants for Phases I–IV significantly shortened with increasing temperature. Curve fitting using h-L functions was significantly better than that using m-E functions for Phases I–IV at all temperatures. Therefore, the superiority of the goodness of h-L fit vs. m-E fit remained at all temperatures. As LV inotropic and lusitropic indices, temperature-dependent h-L time constants could be more useful than m-E time constants for Phases I–IV.
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Trofimiuk-Muldner, Malgorzata, Bartosz Domagala, Michal Koziara, Anna Skalniak, and Alicja Hubalewska-Dydejczyk. "PSAT384 Familial Non-Medullary Thyroid Cancer — Does The Number Of Alanine Residues In The FOXE1 Gene Play A Role?" Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A848. http://dx.doi.org/10.1210/jendso/bvac150.1753.
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Abstract Familial non-medullary thyroid cancer (FNMTC) constitutes about 3–9% of all thyroid cancers. One of the genes believed to predispose to non-syndromic FNMTC is FOXE1. It contains a polyalanine tract (polyAla) with a variable number (11–22) of alanine residues. This length polymorphism could lead to changes in the FOXE1-encoded protein (FOXE1 transcription factor) structure and predispose to papillary thyroid cancer (PTC). The aim of the study was to investigate the relationship between the length of the polyAla tract and the stage of PTC at diagnosis (according to AJCC 8th edition) in patients with FNMTC. The study included 27 patients (from twenty families) with familial PTC (at least two family members were diagnosed with the disease). The length of the polyAla tract of the FOXE1 gene was analyzed. The following numbers of polyAla variants were detected: 11-Ala – 2, 12-Ala – 1, 14-Ala – 23, 16-Ala – 28 alleles. The staging at diagnosis was compared in two groups: less than 16-Ala and at least 16-Ala. The stages of pT1a and pT1a (m) were found in 20 alleles in the less than 16-Ala group, whereas in 16 alleles of the at least 16-Ala group, pT1b-pT2(m) was the most common (p = 0.039). Lymph node metastases were found more frequently in the less than 16-Ala group than in the at least 16-Ala group but this difference was not statistically significant (10 vs. 3 respectively; p = 0.680). Conclusions The analysis of the length of the polyAla tract may be a useful diagnostic tool in predicting the course of PTC in patients with a positive family history. The research was funded by the Jagiellonian University Medical College grant No N41/DBS/000087. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
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Inada, Natsumi, Hitoshi Asakawa, Taiki Kobayashi, and Takeshi Fukuma. "Efficiency improvement in the cantilever photothermal excitation method using a photothermal conversion layer." Beilstein Journal of Nanotechnology 7 (March 10, 2016): 409–17. http://dx.doi.org/10.3762/bjnano.7.36.
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Photothermal excitation is a cantilever excitation method that enables stable and accurate operation for dynamic-mode AFM measurements. However, the low excitation efficiency of the method has often limited its application in practical studies. In this study, we propose a method for improving the photothermal excitation efficiency by coating cantilever backside surface near its fixed end with colloidal graphite as a photothermal conversion (PTC) layer. The excitation efficiency for a standard cantilever of PPP-NCHAuD with a spring constant of ≈40 N/m and a relatively stiff cantilever of AC55 with a spring constant of ≈140 N/m were improved by 6.1 times and 2.5 times, respectively, by coating with a PTC layer. We experimentally demonstrate high stability of the PTC layer in liquid by AFM imaging of a mica surface with atomic resolution in phosphate buffer saline solution for more than 2 h without any indication of possible contamination from the coating. The proposed method, using a PTC layer made of colloidal graphite, greatly enhances photothermal excitation efficiency even for a relatively stiff cantilever in liquid.
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Wang, Jingyuan, Yixiang Li, Yanmei Yang, Yongqiang Li, Mingwen Zhao, Weifeng Li, Jing Guan, and Yuanyuan Qu. "Efficient Helium Separation with Two-Dimensional Metal–Organic Framework Fe/Ni-PTC: A Theoretical Study." Membranes 11, no. 12 (November 26, 2021): 927. http://dx.doi.org/10.3390/membranes11120927.
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Helium (He) is one of the indispensable and rare strategic materials for national defense and high-tech industries. However, daunting challenges have to be overcome for the supply shortage of He resources. Benefitted from the wide pore size distribution, sufficient intrinsic porosity, and high specific surface area, metal–organic framework (MOF) materials are prospective candidates for He purification in the membrane-based separation technology. In this work, through first-principles calculations and molecular dynamics (MD) simulations, we studied the permeability and filtration performance of He by the newly synthesized two-dimensional Fe-PTC MOF and its analogue Ni-PTC MOF. We found that both Fe-PTC and Ni-PTC have superior high performance for He separation. The selectivity of He over N2 was calculated to be ~1017 for Fe-PTC and ~1015 for Ni-PTC, respectively, both higher than most of the previously proposed 2D porous membranes. Meanwhile, high He permeance (10−4~10−3 mol s−1 m−2 Pa−1) can be obtained for the Fe/Ni-PTC MOF for temperatures ranging from 200 to 500 K. Therefore, the present study offers a highly prospective membrane for He separation, which has great potential in industrial application.
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Marotta, Gianluca, Daniela Fontani, Franco Francini, David Jafrancesco, Maurizio De Lucia, and Paola Sansoni. "Laser Profilometry on Micro-PTC." Energies 15, no. 14 (July 21, 2022): 5293. http://dx.doi.org/10.3390/en15145293.
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Profilometry is useful in detecting surface faults on solar concentrators, which can be imperfectly manufactured, thus affecting system performance. Profilometric analyses are performed on a micro-parabolic trough collector (m-PTC), with reduced sizes and greater mirror curvature than a usual PTC. The peculiar dimensions and shape of this micro-PTC request to develop a specific configuration of laser profilometry. It includes a laser diode with a converging lens placed in front of it, ensuring that the mirror curvature does not affect the beam reflection. A new method to calculate the spot position furnishes the reflected beam center even if it lies outside the target, giving it a virtual expansion. The profile is assessed with an iterative calculation, starting from a first point, physically measured. The results are the 3D profile reconstruction of the parabolic mirror and a map of the slope error for each mirror point. It also estimates the intercept factor, a parameter fundamental to optimize the m-PTC system, whose value is in agreement with a structured light measurement on the same object. This intercept factor was obtained averaging the local intercept factor calculated for each mirror point, which individuates the mirror portions not focusing the sunrays on the tube.
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Bhat, Vadisha Srinivas, Marina Saldanha, K. Biniyam, and Harish S. Permi. "Unusual Presentation of Papillary Thyroid Carcinoma." International Journal of Head and Neck Surgery 6, no. 1 (2015): 32–34. http://dx.doi.org/10.5005/jp-journals-10001-1216.
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ABSTRACT Papillary thyroid carcinoma (PTC) has the highest incidence of cervical lymph node metastasis among thyroid malignancies. Lateral neck swelling as the only manifestation of PTC in the absence of palpable thyroid lesion is not common. Here, we report a case of an adult female who presented with right cervical mass and excision biopsy revealed metastatic papillary carcinoma of thyroid. Total thyroidectomy with central compartment neck dissection was performed, and histopathology showed multifocal PTC. How to cite this article Saldanha M, Biniyam K, Permi HS, Bhat VS. Unusual Presentation of Papillary Thyroid Carcinoma. Int J Head Neck Surg 2015;6(1):32-34.
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Matsunaga, Naoki, Nobuhiro Hidaka, Soichiro Sameshima, and Yoshihiro Hirata. "Mechanical Properties of SiC Processed with Nanometer-Sized Powder and Polytitanocarbosilane." Key Engineering Materials 352 (August 2007): 73–76. http://dx.doi.org/10.4028/www.scientific.net/kem.352.73.
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A bimodal powder system of 800 nm SiC (75 vol%) - 30 nm SiC (25 vol%) was dispersed at 20 vol% solid in a 0.3 M Y(NO3)3 solution containing 0.2 μm Al2O3 and 1.0 mg/m2 polyacrylic acid (PAA: dispersant). The SiC (97.6 vol%)-Al2O3 (1.2 vol%)-Y2O3 (1.2 vol%)-PAA system suspension was consolidated by casting in a gysum mold. Polytitanocarbosilane (PTC) of 3 vol% was infiltrated into the SiC compact calcined at 800 °C to increase the mechanical properties and Weibull modulus. Both the calcined powder compacts with and without PTC were hot-pressed to relative density above 97 % at 1950 °C. The hot-pressed SiC with or without PTC provided the following excellent mechanical properties: average four-point flexural strength of 911 and 812 MPa, fracture toughness of 5.2 and 6.0 MPa·m1/2, and Weibull modulus 11.3 and 5.8 for PTC addition and no addition, respectively. The PTC addition was effective to decrease the shape factor of flaw and increased the strength and Weibull modulus.
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Sookramoon, Krissadang. "Design, Constructand Performance Evaluation of a 2-Stage Parabolic through Solar Concentrator in Pathumthani." Advanced Materials Research 931-932 (May 2014): 1291–97. http://dx.doi.org/10.4028/www.scientific.net/amr.931-932.1291.
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This research presents the design, construct and performance evaluation of a 2-stage parabolic trough solar concentrator (2-stage PTC). The primary stage was constructed of polished stainless steel (SUS 400) to form the primary stage parabolic reflector (1.489 m ×1.489 m size), the second stage was constructed of multi piece mirror to form the hyperbolic shape reflector (0.13 m×1.489 m). Black painted copper pipe in the size of inside diameters (27.2 mm) covered with glass tube was used as receiver. One axis Sun tracking system has been installed to track 2-stage PTC according to the direction of beam propagation of solar radiation. By using water as a heat transfer fluid its capability to heat transfer and load high temperature (100°C). The storage tank is fabricated with stainless steel of size 40 L. The experimental tests have been carried out in Faculty of Industrial Technology, Vallaya Alongkorn Rajabhat University Pathum Thani, Thailand climatic conditions (14.134°N, 100.611°E) during 5 selected days of the months May 2013. The performance of a 2-stage PTC was evaluated using outdoor experimental measurements including the useful heat gain, the thermal instantaneous efficiency and the energy gained by the water. The experimental results shown the maximum thermal efficiency was 23.43%, the optical efficiency was 76%, and the total geometrical concentration was 27.08X.
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Farias Neto, João Tomé de, Charles Roland Clement, and Marcos Deon Vilela de Resende. "Estimativas de parâmetros genéticos e ganho de seleção para produção de frutos em progênies de polinização aberta de pupunheira no estado do Pará, Brasil." Bragantia 72, no. 2 (June 2013): 122–26. http://dx.doi.org/10.1590/s0006-87052013000200002.
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O estudo objetivou estimar parâmetros e valores genéticos para os caracteres número de cachos (NC), peso médio do cacho (PMC) e peso total do cacho (PTC) aos seis anos, pelo método de modelos mistos (REML/BLUP). O teste de progênies foi estabelecido sob o delineamento de blocos ao acaso com 50 tratamentos (progênies), 10 blocos e uma planta por parcela, no espaçamento de 5 x 5 m, além de uma bordadura externa ao experimento. As estimativas de herdabilidade individual e médias no sentido restrito para PTC (0,213 e 0,360) e NC (0,286 e 0,435), respectivamente, foram de boas magnitudes. O coeficiente de variação genética individual exibiu valores elevados para PTC (19,86) e NC (17,59). A raiz quadrada da herdabilidade ao nível de médias das progênies resulta em acurácia seletiva na ordem de 0,60 para PTC e 0,66 para NC, atestando boa precisão e confiança nos parâmetros genéticos estimados, promovendo segurança na seleção. O potencial da população para fins de melhoramento pode ser observado por meio dos ganhos genéticos para PTC, que oscilaram de 8,3 a 19,9 kg, elevando a nova média populacional para o caráter após um ciclo de seleção, para 40,4 kg, equivalente a 25,8%.
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Hyogo, Yasuko, Naomi Kiyota, Naoki Otsuki, Shunsuke Goto, Yoshinori Imamura, Naoko Chayahara, Masanori Toyoda, et al. "Thrombotic Microangiopathy with Severe Proteinuria Induced by Lenvatinib for Radioactive Iodine-Refractory Papillary Thyroid Carcinoma." Case Reports in Oncology 11, no. 3 (November 12, 2018): 735–41. http://dx.doi.org/10.1159/000494080.
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Standard therapy for radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) is multi-targeted kinase inhibitors (m-TKIs), represented by sorafenib and lenvatinib. One of the main target molecules of m-TKIs is vascular endothelial growth factor receptor (VEGF-R). m-TKIs are known to cause adverse reactions such as hypertension and proteinuria as a class effect. In particular, proteinuria is thought to result from vascular endothelial damage and podocytopathy in glomeruli, and the development of thrombotic microangiopathy (TMA) has been reported for VEGF inhibitors. We encountered a patient with RAI-refractory (RR) papillary thyroid carcinoma (PTC) who developed proteinuria and renal dysfunction due to lenvatinib. Renal biopsy demonstrated that these changes were caused by TMA. To our knowledge, this is the first reported case of TMA due to lenvatinib in a Japanese patient with RR-PTC. A 70-year-old woman developed proteinuria, renal impairment and hypertension while receiving lenvatinib for RR-PTC. Her proteinuria and renal damage continued to worsen despite dose reductions and dose interruptions. Renal biopsy was consistent with the chronic type of TMA. These findings indicate that TMA is a possible cause of proteinuria due to lenvatinib, as has been reported for the VEGF inhibitors.
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Simeakis, George Konstantinou, Ioanna Patinioti, Elli Anagnostou, Evangelia Zapanti, Vasiliki Vasileiou, Antonis Polymeris, Katerina Saltiki, Eleni Anastasiou, Maria Alevizaki, and Marina Mitropoulou. "Association of serum calcitonin levels with multinodular thyroid disease: 10-year single center experience." Problems of Endocrinology 62, no. 5 (September 22, 2016): 54. http://dx.doi.org/10.14341/probl201662554.
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Background. From 2005 to 2015 routine calcitonin (CT) screening was performed in our department in all patients with multinodular goiter (MNG) using the same assay.Aim. We investigated possible associations between unstimulated serum CT levels and the presence of either thyroid autoimmunity (AITD) or thyroid neoplasia.Methods. This is a retrospective study of 648 patients (559 female [F] 86.3%, 89 male [M] 13.7%, age range 18-89, median 58 years,). CT≤4.6 pg/ml [F] and ≤11.5 pg/ml [M] was defined as normal. Patients were stratified into 4 groups according to CT. Group1: CT<0.05 (undetectable), Group2: CT [F&M] within normal range, Group3: CT:4.7-10 [F] & 11.6-20 [M], Group4: CT>10 [F] & >20 [M]. Furthermore patients were subcategorized in those with Autoimmune Thyroid Disease (AITD) and those without (non-AITD).Results. The distribution of patients was: Group1: n=186 (28.7%), Group2: n=422 (65.1%), Group3: n=29 (4.5%), Group4: n=11 (1.7%). Of the patients with AITD history 23.4% belonged to Group1, 68.6% to Group2, 6.4% to Group3 and 1.6% to Group4 (x2, p=0.037). Forty seven patients (7.3%) underwent total thyroidectomy. Histopathological examination revealed: Medullary Thyroid Carcinoma (MTC) n=3 (3/3 Group4), C-Cell Hyperplasia (CCH) n=5 (3/5 Group3, 2/5 Group4), Papillary Thyroid Carcinoma (PTC) n=17 (7/17 Group1, 10/17 Group2), MNG n=22 (8/22 Group1, 10/22 Group2, 2/22 Group3, 2/22 Group4). 2/5 patients with CCH had PTC. 1/17 PTC patient had mixed PTC-MTC. Patients with MTC had remarkably higher CT levels (253-1222 pg/ml) compared to those with CCH (5.8-16.1 pg/ml).Conclusions. This study reaffirms the positive correlation between CT levels and the presence of MTC or CCH, clearly and conspicuously distinguished by the range of CT levels, albeit in a small number of patients with these diagnoses. Patients with AITD have more frequently detectable or slightly increased CT levels.
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Wang, Huijuan, Pingping Wang, Yu Wu, Xiukun Hou, Zechun Peng, Weiwei Yang, Lizhao Guan, et al. "Correlation between obesity and clinicopathological characteristics in patients with papillary thyroid cancer: a study of 1579 cases: a retrospective study." PeerJ 8 (September 8, 2020): e9675. http://dx.doi.org/10.7717/peerj.9675.
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Objective To explore the relationship between body mass index (BMI) and clinicopathological characteristics in patients with papillary thyroid carcinoma (PTC). Methods The clinical data of 1,579 patients with PTC, admitted to our hospital from May 2016 to March 2017, were retrospectively analyzed. According to the different BMI of patients, it can be divided into underweight recombination (BMI < 18.5 kg/m), normal body recombination (18.5 ≤ BMI < 24.0 kg/m2), overweight recombination (24.0 ≤ BMI < 28.0 kg/m2) and obesity group (BMI ≥ 28.0 kg/m2). The clinicopathological characteristics of PTC in patients with different BMIs group were compared. Results In our study, the risk for extrathyroidal extension (ETE), advanced T stage (T III/IV), and advanced tumor-node-metastasis stage (TNM III/IV) in the overweight group were higher, with OR (odds ratio) = 1.99(1.41–2.81), OR = 2.01(1.43–2.84), OR = 2.94(1.42–6.07), respectively, relative to the normal weight group. The risk for ETE and T III/IV stage in the obese group were higher, with OR = 1.82(1.23–2.71) and OR = 1.82(1.23–2.70), respectively, relative to the normal weight group. Conclusion BMI is associated with the invasiveness of PTC. There is a higher risk for ETE and TNM III/IV stage among patients with PTC in the overweight group and for ETE among patients with PTC in the obese group.
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Sosnin, Dmitriy Yu, Ol'ga Yu Nenasheva, Nadezhda A. Zubareva, Andrey V. Renzhin, and Konstantin R. Gal'kovich. "Urinary and blood procalcitonin concentration in healthy persons." Perm Medical Journal 36, no. 5 (December 21, 2019): 35–43. http://dx.doi.org/10.17816/pmj36535-43.
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Aim. Blood serum and urinary procalcitonin (PCT) concentration in healthy persons was studied.
Materials and methods. A single-stage observational study of case-control type was performed. The study included 32 men and 37 women of middle age (53.4 16.4 years) with normal renal function. PTC concentration was determined with the method of solid-phase enzyme immunoassay using test-system (Procalcitonin IFA-BEST, Russia).
Results. Blood serum PCT concentration in the examined persons was 0.029 0.016 ng/ml (M SD). The number of blood serum samples with PTC level 0.05 ng/ml was 5.8 % (4 from 69). The mean urinary PTC concentration by 72.59 times exceeded the mean blood serum PTC content and was 2.12 1.832 ng/ml (р 0.000001).
Coefficient of variation of results for the urine by 1.57 times exceeded the analogous index for the blood serum. When comparing the results of blood serum and urine analyses, no statistically significant differences between men and women were revealed. When estimating the coefficients of linear correlation between PTC content in the blood serum and urine, a weak positive dependence was established (R = 0.302782).
Conclusions. High PTC concentration in the urine permits to suppose that one of the ways of procalcitonin removal from the blood plasma is its elimination by kidneys in unchanged type by means of glomerular filtration.
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Achouri, Intissar, Mouhamed Elbar Soudani, and Tlili Salah. "The efficiency of steam production by the Parabolic Trough Collector PTC with the use of nanofluids in the region of Ouargla." IOP Conference Series: Materials Science and Engineering 1204, no. 1 (November 1, 2021): 012005. http://dx.doi.org/10.1088/1757-899x/1204/1/012005.
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Abstract Concentrated solar power plants (CSP) contribute to global production (at present) with a capacity of 400 MW, and by 2020 they will reach approximately 20 GW, then nearly 800 GW by 2050, This will prevent the emission of 32 million tons of CO2 annually in 2020, and rise to 1.2 billion tons in 2050, according to the International Greenpeace “Solar Thermal Electricity” 2016 report. Among all the concentrated solar power (CSP) technology available to date, Parabolic Trough Collector (PTC) is the most promising, cost-effective, and efficient solution to generating electrical power, as PTC plants contribute in terms of global production capacity by 73.58% of the overall capacity of concentrated solar power plants (CSP). PTC stations in the production of electricity depend on the generation of hot and pressurized steam that rotates the turbines and to increase the effectiveness of PTC in the production of steam, we use in this study nanofluids by adding copper nanomaterials in different proportions to improve the Thermal efficiency of PTC. We also studied the effect of the width of the PTC slot on the fluid temperature. And from it on the amount of steam produced. The results of the study showed that the Thermal efficiency increases with the increase in the ratio of copper nanomaterials in the water, as the temperature of outlet water reaches 98°C, for the ratio of nanomaterials, 20%, in order to water flow 0.01 Kg/s and display the aperture 3.5 m.
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Zhong, Cheng, Kensuke Kayamori, Shuhei Koide, Daisuke Shinoda, Motohiko Oshima, Yaeko Nakajima-Takagi, Yurie Nagai, et al. "Efficacy of Tubulin Polymerization Inhibitor in Myelodysplastic Syndrome." Blood 136, Supplement 1 (November 5, 2020): 35. http://dx.doi.org/10.1182/blood-2020-134754.
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Background: Myelodysplastic Syndrome (MDS) is a clonal bone marrow disorder characterized by ineffective and clonal hematopoiesis accompanied by morphological dysplasia and variable cytopenia. There are few treatment options for MDS, and allogenic hematopoietic stem cell transplantation is the only curative option. Tubulin belongs to protein superfamily of globular proteins. Monomeric tubulin can polymerize into microtubules, which play an important role in the attachment and segregation of chromosomes in various phases of cell division. Therefore, the targeting of microtubules represents a therapeutic strategy against both solid and hematological cancers. The first approved tubulin binding agent by the FDA was vincristine, which has been clinically used to treat multiple types of cancers, particularly hematological malignancies. Over the past few decades, additional tubulin binding agents have been developed and received FDA approval, mostly for applications to cancer therapy. These agents have been classified by their binding sites on tubulin, which influences their roles in the inhibition or stabilization of polymerized microtubules. We herein investigated the efficacy of PTC-028, a novel microtubule polymerization inhibitor for MDS. Method: Anti-MDS efficacy of PTC-028 was studied using human MDS cell lines and primary MDS cells in vitro. The efficacy of PTC-028 was also assessed in a xenograft mouse model of MDS using an MDS cell lines. PTC-028 was synthesized at PTC Therapeutics Inc. Mechanistic studies were conducted via flow cytometry and RNA sequencing. Results: A previous study reported that PTC596 suppressed cell proliferation and induced apoptosis in AML cell lines. Since MDS is regarded as a pre-leukemic stage, we examined the effects of PTC-028, another novel microtubule polymerization inhibitor, on MDS cells. PTC-028 induced a dose-dependent inhibition of cell proliferation on MDS cell lines, such as MDS-L and SKM-1 cells. Caspase 3/7 activity was also significantly induced in MDS-L and SKM-1 cells in the presence of PTC-028, suggesting the induction of apoptotic cell death by PTC-028. We then isolated CD34+ cells from primary MDS BM samples and investigated the efficacy of PTC-028 on primary MDS cells. The efficacy of PTC-028 in CD34+ MDS cells was also confirmed by cell proliferation assays. To enhance the therapeutic benefit of PTC-028 on MDS cells, we investigated synergism between PTC-028 and DNA hypomethylating agents. We treated MDS-L and SKM-1 cells with PTC-028 in combination with DNA hypomethylating agents. After 3 days of culture, cell growth was analyzed by MTS and Annexin V assays. PTC-028 synergized with hypomethylating agents, such as decitabine and azacitidine, to inhibit the growth and induce apoptosis of MDS cells. We assessed the efficacy of PTC-028 in a xenograft mouse model of MDS using an MDS cell line. Recipient mice were treated with PTC-028 for 7 weeks. PTC-028 significantly inhibited the growth of MDS-L cells and prolonged the overall survival of recipient mice. Furthermore, a significant synergistic effect was observed between PTC-028 and decitabine. Mice that received combination therapy showed moderate weight loss 11 days after the initiation of the treatment, but subsequently recovered. Mechanistically, a treatment with PTC-028 induced G2/M arrest followed by apoptotic cell death. We then investigated the effect of PTC-028 on the levels of soluble (unpolymerized) versus polymerized tubulin in MDS-L cells. Cells were treated with PTC-028 and paclitaxel for 4 hours, and cell lysates were then separated into soluble and polymerized fractions by centrifugation. The visualization of tubulin fractions by Western blotting demonstrated that the PTC-028 treatment for 4 hours resulted in the near-complete loss of polymerized microtubules. In contrast, polymerized microtubules increased in cells treated with paclitaxel, which stabilizes microtubules against depolymerization. These result indicates that PTC-028 also acts as a microtubule polymerization inhibitor. Conclusion: Our data reveal a possible chemotherapeutic strategy for PTC-028 and PTC-596 in MDS by disruption of microtubule dynamics as a single agent and in combination with hypomethylating agents. The present study provides a preclinical framework for the clinical evaluation of this promising therapeutic approach to improve outcomes in MDS patients. Disclosures Lennox: PTC therapeutics: Current Employment. Sheedy:PTC therapeutics: Current Employment. Weetall:PTC Therapeutic: Current Employment.
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Skibiel, C., S. Ren, and L. Reid. "NTRK3-rearranged thyroid carcinoma, clinical and pathologic features." American Journal of Clinical Pathology 156, Supplement_1 (October 1, 2021): S50. http://dx.doi.org/10.1093/ajcp/aqab191.101.
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Abstract Introduction/Objective NTRK3 gene encodes a transmembrane protein receptor of the tropomyosin receptor kinase (Trk) family. Gene fusions involving NTRK3 result in a constitutive activation or overexpression of Trk receptor, potentially leading to oncogenesis. NTRK targeted therapies show a promising activity in varied cancer types with NTRK fusions. The aim of this case review is to describe the clinical and pathologic findings of thyroid neoplasm with NTRK3 gene fusions. Methods/Case Report The cytology fine needle aspiration (FNA), molecular testing results and pathology of surgical resections are reviewed in 220 cases of total and hemithyroidectomy from January 2018 to May 2021. Results (if a Case Study enter NA) Three cases with NTRK3 gene fusions are identified by Thyroseq or Afirma GSC from FNA of thyroid nodules with later surgical intervention. No other mutations or gene fusions were identified. Each case had total thyroidectomy. Case 1 is a 41-year-old female with FNA diagnosis of suspicious for papillary thyroid carcinoma (PTC) and ETV6/NTRK3 fusion found by Afirma GSC. Pathology diagnosis is PTC classic type, two tumor nodules 1.1cm and 1.0cm, lymphovascular invasion not identified, three lymph nodes not involved by tumor and pathologic stage pT1b(m) pN0. Case 2 is a 49-year-old female with FNA diagnosis of atypia of undetermined significance and ETV6/NTRK3 fusion detected by Thyroseq. Pathology diagnosis is infiltrative PTC follicular variant, 2.0cm, angioinvasion present, no lymph nodes submitted and pathologic stage pT1b(m) pNX. Case 3 is a 28-year-old female with FNA diagnosis of suspicious for follicular derived neoplasm and NTRK3/RBPMS fusion is detected by Afirma GSC. Pathology diagnosis is infiltrative PTC follicular variant, 1.5cm, 9 of 11 lymph nodes positive for metastatic carcinoma and pathologic stage pT1b pN1b. Conclusion Thyroid neoplasm with NTRK3-rearrangement is rare. Cases 1 and 2 with common ETV6-NTRK3 fusion show PTC classic type and infiltrative PTC follicular variant with angioinvasion. Case 3 with less common NTRK3/RBPMS fusion shows infiltrative PTC follicular variant and significant lymph node involvement. Our limited cases of NTRK3-rearranged thyroid carcinoma demonstrate infiltrative growth, diverse phenotypes, one case with angioinvasion and no lymph nodes submitted and one case with multiple lymph node metastasis. This suggests aggressive behavior of thyroid cancer with NTRK3 gene fusion and patients may benefit from targeted NTRK therapy.
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Yang, Meng Meng, Zhi Jian Peng, Cheng Biao Wang, and Xiu Li Fu. "Influence of (Bi0.5M0.5)TiO3 (M=Li, Na, K, Rb) Addition on the Curie Temperature and PTC Effect of BaTiO3-Based Ceramics." Key Engineering Materials 697 (July 2016): 239–42. http://dx.doi.org/10.4028/www.scientific.net/kem.697.239.
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In order to investigate the influence of (Bi0.5M0.5)TiO3 (M=Li, Na, K, Rb) addition on the Curie temperature (Tc) and positive temperature coefficient (PTC) effect of BaTiO3-based ceramics, BaTiO3-(Bi0.5M0.5)TiO3 (M=Li, Na, K, Rb) solid solutions were prepared by a conventional solid sintering reaction using high-purity reagents. It was found that the Tc of the samples would vary with (Bi0.5M0.5)TiO3 of different alkali ions, in which BT-BKT ceramics had the highest value (about 148 °C). Moreover, the incorporation of alkali ions would influence the PTC effect of the sample, which can be defined by the resistivity jump with the ratio of maximum to minimum resistivity (ρmax/ρmin). Under the present conditions, the ρmax/ρmin of BT-BRT and BT-BLT ceramics were almost equal and higher than those of BT-BNT and BT-BKT ceramics.
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Li, Wei, Qing Huang, Danyang Sun, Guizhi Zhang, and Jian Tan. "RDM1 gene overexpression represents a therapeutic target in papillary thyroid carcinoma." Endocrine Connections 6, no. 8 (November 2017): 700–707. http://dx.doi.org/10.1530/ec-17-0209.
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RAD52 motif containing 1 (RDM1) encodes the RAD52 protein involved in DNA double-strand break repair and recombination events. However, the importance of RDM1 in papillary thyroid carcinoma (PTC) is largely unknown. In the present study, we examined the role of RDM1 in thyroid cancer. The RDM1 expression in PTC patients was examined using immunohistochemistry. The expression levels of RDM1 mRNA in thyroid cancer cells were measured by quantitative real-time PCR (qRT-PCR). Lentivirus-mediated small interfering RNAs (siRNAs) were used to knock down the RDM1 expression in the K1 and TPC1 cells. Then, changes in the RDM1 target gene expression were determined by qRT-PCR and Western blot. Cell proliferation was examined by a high content screening assay. Cell cycle distribution and apoptosis were detected by flow cytometric analysis and MTT analysis. We showed that the RDM1 expression was higher in PTC tissue compared to pericarcinous tissue. RDM1 mRNA was found to be expressed by qRT-PCR. Using a lentivirus-based RNA interference (RNAi) approach, the RDM1 expression was significantly inhibited. The inhibition of RDM1 expression by RNAi significantly impaired cell proliferation, increased apoptosis and arrested cells in the G2/M phase. These data showed that RDM1 was highly expressed in PTC tissue and thyroid cancer cell lines. Moreover, RDM1 may play an important role in cell proliferation, cell cycle distribution and apoptosis of human PTC cells.
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Wang, Xinpei, Xiujie Cui, Qian Zhao, Feifei Sun, Ru Zhao, Tingting Feng, Shaofeng Sui, Bo Han, and Zhiyan Liu. "Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß." Cancers 14, no. 11 (June 2, 2022): 2772. http://dx.doi.org/10.3390/cancers14112772.
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Polybrominated diphenyl ethers (PBDEs) have been reported to possess endocrine-disrupting and tumour-promoting activity. However, the effects of long-term exposure to decabromodiphenyl ether (BDE209) on thyroid tumourigenesis of papillary thyroid carcinoma (PTC) and the underlying mechanisms remain poorly defined. In this study, functional assays in vitro and mouse models in vivo were used to evaluate the toxic effects of long-term exposure to environmental concentrations of BDE209 on the pathogenesis and progression of PTC. MTS, EdU and colony-forming assays confirmed the chronic toxicity of BDE209 on the proliferation of human normal follicular epithelial cell line (Nthy-ori 3-1) and PTC-derived cell lines (TPC-1 and BCPAP). Wound and Transwell assays showed that BDE209 exacerbated the aggressiveness of PTC cells. BDE209 significantly promoted cell proliferation during the S and G2/M phases of the cell cycle. Mechanistically, BDE209 altered the thyroid system by acting as a competitive inhibitor of thyroid receptor beta (TRß) expression and function, which was further proven by public databases and RNA-seq bioinformation analysis. Taken together, these results demonstrated that BDE209 has chronic toxicity and potential tumourigenic effects on the thyroid by inhibiting TRß.
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Ng´ang´a, Peter Njenga, Julia K. Ebner, Matthias Plessner, Klaus Aktories, and Gudula Schmidt. "Engineering Photorhabdus luminescens toxin complex (PTC) into a recombinant injection nanomachine." Life Science Alliance 2, no. 5 (September 20, 2019): e201900485. http://dx.doi.org/10.26508/lsa.201900485.
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Engineering delivery systems for proteins and peptides into mammalian cells is an ongoing challenge for cell biological studies as well as for therapeutic approaches. Photorhabdus luminescens toxin complex (PTC) is a heterotrimeric protein complex able to deliver diverse protein toxins into mammalian cells. We engineered the syringe-like nanomachine for delivery of protein toxins from different species. In addition, we loaded the highly active copepod luciferase Metridia longa M-Luc7 for accurate quantification of injected molecules. We suggest that besides the probable size limitation, the charge of the cargo also influences the efficiency of packing and transport into mammalian cells. Our data show that the PTC constitutes a powerful system to inject recombinant proteins, peptides, and potentially, other molecules into mammalian cells. In addition, in contrast to other protein transporters based on pore formation, the closed, compact structure of the PTC may protect cargo from degradation.
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Sainsbury, Elliott M., Reinhard K. H. Schiemann, Kevin I. Hodges, Alexander J. Baker, Len C. Shaffrey, and Kieran T. Bhatia. "Why Do Some Post-Tropical Cyclones Impact Europe?" Monthly Weather Review 150, no. 10 (October 2022): 2553–71. http://dx.doi.org/10.1175/mwr-d-22-0111.1.
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Abstract Post-tropical cyclones (PTCs) can bring high winds and extreme precipitation to Europe. Although the structure and intensity of observed Europe-impacting PTCs has been investigated in previous studies, a quantitative understanding of the factors important for PTCs to reach Europe has not been established. By tracking and identifying the full life cycle of tropical cyclones (TCs) in the ERA5 reanalysis, we investigate why some PTCs impact Europe and why others do not, using a composite analysis. We show that PTCs that impact Europe are typically ∼4–6 m s−1 stronger at their lifetime maximum intensity and throughout the extratropical transition process. They are also twice as likely to reintensify in the midlatitudes. During ET, the Europe-impacting PTCs interact more strongly with an upstream upper-level trough in a significantly more baroclinic environment. The Europe-impacting PTCs are steered on a more poleward trajectory across a midlatitude jet streak. It is during the crossing of the jet that these cyclones often undergo their reintensification. Using contingency table analysis, TC lifetime maximum intensity, and whether post-ET reintensification occurs are shown to be significantly associated with the odds that a PTC reaches Europe. This supports our composite analysis and further indicates that TC intensity and reintensification both modulate the likelihood that a PTC will impact Europe. Significance Statement Some post-tropical cyclones (PTCs) reach Europe, often associated with extreme precipitation and high winds. It is currently unclear what factors allow this to occur. In this study, we track cyclones in two reanalyses using a feature tracking scheme and identify the PTCs by matching (in space and time) reanalysis tracks with observed tracks. Using a composite analysis, we show that 1) tropical cyclones (TCs) that are more intense, and 2) TCs that reintensify after extratropical transition, are more likely to reach Europe. TCs that reintensify interact strongly with an upper-level upstream trough and cross a midlatitude jet streak. Reintensification occurs as the cyclones cross this jet streak.
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Duan, Y. B., J. Wang, S. S. Wu, W. Wang, R. J. Huang, L. F. Li, and Y. Zhou. "Application of Stirling pulse tube cryocoolers in high temperature superconducting filters subsystems." IOP Conference Series: Materials Science and Engineering 1240, no. 1 (May 1, 2022): 012133. http://dx.doi.org/10.1088/1757-899x/1240/1/012133.
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Abstract The application of high temperature superconducting(HTS)filter has penetrated into various fields. In recent decades, GM-type pulse tube cryocooler and Stirling-type pulse tube cryocooler (SPTC) are two common cryocoolers. Due to the advantages of PTCs, such as no moving parts at the cold end, simple structure, small mechanical vibration and longer lifetime, pulse tube cryocoolers is gradually replacing oil-lubricated Stirling-coolers and G-M cryocoolers to cool down HTS magnets. In this paper, the development of PTC in HTS magnet cooling in the past 20 years is summarized firstly. Secondly, the development of HTS cooling system in our lab are reported. At last, the further development direction of HTS’s cooling system is discussed.
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Shen, Yanbing, Wenfei He, Dan Wang, Ding Cao, Hongliang Mei, Tianji Luan, and Yilin Hu. "Identification of Gene Coexpression Modules and Prognostic Genes Associated with Papillary Thyroid Cancer." Journal of Oncology 2022 (September 20, 2022): 1–14. http://dx.doi.org/10.1155/2022/9025198.
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Thyroid cancer is a great part of the endocrine tumor with an increasing incidence. Papillary thyroid carcinoma (PTC) is the most common subtype. With the enormous pace taken in the microarray technology, bioinformatics is applied in data mining more frequently. Weighted gene coexpression network analysis (WGCNA) can perform analysis combining clinic information. We performed WGCNA for prognostic genes associated with PTC. From the GEO profile, we got ten modules. We identified a key module that was closest to patients’ survival time. Then, we screened five hub genes (ATRX, BOD1L1, CEP290, DCAF16, and NEK1) from the key module based on the clinical information from TCGA. These five genes not only significantly differ between the normal and tumor groups but have prognostic value. The receiver operating characteristic (ROC) curve indicated that they had the potential to serve as prognostic genes. We performed next-generation sequencing using the PTC tissue to get more convincing evidence. Besides, we established a new signature and verified it through K-M plots and ROC. The signature could be an independent factor for the prognosis of PTC, and we built a nomogram to carry out a quantitative study. In a word, the hub genes we explored in the study deserved more basic and clinical research.
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Khachatryan, Anna R., Goar J. Vardanyan, Garnik A. Avetisyan, Aram S. Chomoyan, Satenik E. Baghdasaryan, and Kristina A. Porksheyan. "Peculiarities of sonoelastographic imaging of thyroid papillary cancer in presence of autoimmune thyroiditis." Terapevticheskii arkhiv 93, no. 4 (April 15, 2021): 369–75. http://dx.doi.org/10.26442/00403660.2021.04.200675.
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Aim. To determine the features of visualization of papillar thyroid cancer (PTC) in presence of autoimmune thyroiditis (AIT) according to sonoelastography data.
Materials and methods. 155 patients were examined (75 PTC, 30 AIT, 20 PTC in presence of AIT and 30 with diffuse parenchymal changes) and 30 patients of the control group. Among patients with PTC 68 (90.7%) were represented by female (mean age 46.713.12 years) and 7 (9.3%) by male (average age 48.14.05 years) patients, PTC in presence of AIT by 19 female (average age 46.916.98 years) and 1 male (22 years) patients. Ultrasound investigation was performed with devices Toshiba Aplio-400 and Toshiba Aplio-500 (Japan) by the standard method and using elastography. A surface transducer with a frequency of 1014 MHz was used. An analysis of the thyroid ultrasound image was performed in correspondence with TI-RADS. For a qualitative assessment of the elastographic picture of thyroid foci, the TsukubaUeno assessment visual standardized system was implemented.
Results. According to the TI-RADS scale, most nodular formations are assigned to category 4. With TPC with an unchanged thyroid gland, category 4 was determined in 52 patients (69.3%), and with PR in presence of AIT 15 patients (75%). When determining the qualitative criteria for Tsukuba Ueno, the majority of tumors were assigned to types 3b and 4: cancers in presence of AIT 95% and cancers with no changes to thyroid gland 81.3%. Sonoelastographic criteria for thyroid parenchyma with AIT with a high degree of confidence are significantly higher than in the control group (p0.000). In a comparative analysis of thyroid sonoelastography in PTC with unchanged parenchyma and AIT, changes according to compression elastography are statistically unreliable. In shear wave elastography, sonoelastographic criteria for PTC are significantly higher in patients with AIT (p0.02 when measured in kPa, p0.01 when measured in m/s).
Conclusion. Sonoelastography data can be used as additional criteria in the differential diagnosis of focal thyroid formations.
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Wang, Qiliang, Hongxing Yang, Gang Pei, Honglun Yang, Jingyu Cao, and Mingke Hu. "Assessment of Performance Enhancement Potential of a High-Temperature Parabolic Trough Collector System Combining the Optimized IR-Reflectors." Applied Sciences 10, no. 11 (May 28, 2020): 3744. http://dx.doi.org/10.3390/app10113744.
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Heat collecting elements (HCEs) are the core components in the parabolic trough collector (PTC) system because photothermal conversion of the whole system occurs in the HCEs. However, considerable heat loss from the HCEs at high operating temperature exerts seriously negative impact on the photothermal conversion efficiency of the PTC system and subsequent application systems. To effectively reduce the heat loss and thus enhance the overall performance of the PTC system, in our previous work, we proposed three kinds of novel HCEs by partially depositing different IR-reflector coatings on the inner and outer surfaces of the glass envelope. The infrared (IR)-reflector of actual transparent conductive oxide (TCO) film, IR-reflector with a fixed cutoff wavelength of 2.5 μm, and the IR-reflector with optimal cutoff wavelength showed extremely effective roles in the reduction of heat loss in HCEs. In this paper, the comprehensive energy and exergy performances of these three novel HCEs in a real 72 m small-scale PTC system are further investigated by the mathematical models established. Additionally, the comparisons among overall performances of the proposed HCEs under different direct solar irradiances are also carried out. The results show that the simulated data yields good consistence with the experimental results, and that all three of the novel HCEs achieve superior overall performance compared with the conventional HCEs. The PTC system installing the novel HCEs with the IR-reflector coating which possesses the optimal cutoff wavelength has the best energetic and exergetic efficiencies, which are significantly improved by 25.2% and 28.1% compared with the conventional HCEs at the solar irradiance of 800 W/m2 and inlet temperature of 580 °C. Moreover, the proposed novel HCEs have a much superior performance at lower solar irradiance. The performance-enhanced PTC system will play a significantly positive role in the performance improvement of the heating and cooling of buildings in the future.
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Nakase, Takanobu, Kenta Ariga, Wenxiang Meng, Motoki Iwasaki, Tetsuya Tomita, Akira Myoui, Kazuo Yonenobu, and Hideki Yoshikawa. "Distribution of genes for parathyroid hormone (PTH)—related peptide, Indian hedgehog, PTH receptor and patched in the process of experimental spondylosis in mice." Journal of Neurosurgery: Spine 97, no. 1 (July 2002): 82–87. http://dx.doi.org/10.3171/spi.2002.97.1.0082.
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Object. Little is known about the molecular mechanisms underlying the process of spondylosis. The authors determined the extent of genetic localization of major regulators of chondrogenesis such as Indian hedgehog (Ihh) and parathyroid hormone (PTH)—related peptide (PTHrP) and their receptors during the development of spondylosis in their previously established experimental mouse model. Methods. Experimental spondylosis was induced in 5-week-old ICR mice. The cervical spines were chronologically harvested, and histological sections were prepared. Messenger (m) RNA for PTHrP, Ihh, PTH receptor (PTHR; a receptor for PTHrP), patched (Ptc; a receptor for Ihh), bone morphogenetic protein (BMP)—6, and collagen type X (COL10; a marker for mature chondrocyte) was localized in the tissue sections by performing in situ hybridization. In the early stage, mRNA for COL10, Ihh, and BMP-6 was absent; however, mRNA for PTHrP, PTHR, and Ptc was detected in the anterior margin of the cervical discs. In the late stage, evidence of COL10 mRNA began to be detected, and transcripts for Ihh, PTHrP, and BMP-6 were localized in hypertrophic chondrocytes adjacent to the bone-forming area in osteophyte. Messenger RNA for Ptc and PTHR continued to localize at this stage. In control mice, expression of these genes was absent. Conclusions. The localization of PTHrP, Ihh, BMP-6, and the receptors PTHR and Ptc demonstrated in the present experimental model indicates the possible involvement of molecular signaling by PTHrP (through the PTHR), Ihh (through the Ptc), and BMP-6 in the regulation of chondrocyte maturation leading to endochondral ossification in spondylosis.
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Aram, Farshid, Ebrahim Solgi, Ester Higueras García, Amir Mosavi, and Annamária R. Várkonyi-Kóczy. "The Cooling Effect of Large-Scale Urban Parks on Surrounding Area Thermal Comfort." Energies 12, no. 20 (October 15, 2019): 3904. http://dx.doi.org/10.3390/en12203904.
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This empirical study investigates large urban park cooling effects on the thermal comfort of occupants in the vicinity of the main central park, located in Madrid, Spain. Data were gathered during hot summer days, using mobile observations and a questionnaire. The results showed that the cooling effect of this urban park of 125 ha area at a distance of 150 m could reduce air temperatures by an average of 0.63 °C and 1.28 °C for distances of 380 m and 665 meters from the park. Moreover, the degree of the physiological equivalent temperature (PET) index at a distance of 150 meters from the park is on average 2 °C PET and 2.3 °C PET less compared to distances of 380 m and 665 m, respectively. Considering the distance from the park, the correlation between occupant perceived thermal comfort (PTC) and PET is inverse. That is, augmenting the distance from the park increases PET, while the extent of PTC reduces accordingly. The correlation between these two factors at the nearest and furthest distances from the park is meaningful (p-value < 0.05). The results also showed that large-scale urban parks generally play a significant part in creating a cognitive state of high-perceived thermal comfort spaces for residents.
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Lóránt, Bálint, Krisztina László, and Gábor Márk Tardy. "Improving the Performance of Microbial Fuel Cells with Modified Carbon Aerogel Based Cathode Catalysts." Periodica Polytechnica Chemical Engineering 66, no. 1 (November 26, 2021): 1–9. http://dx.doi.org/10.3311/ppch.18854.
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Microbial fuel cells (MFCs) are capable of converting the chemical energy of biodegradable organic matter directly into electricity, thus they can be applied in various fields: waste elimination, biosensor industry and production of renewable energy. In this study, the efficiency of noble metal free carbon aerogel based cathode catalysts was investigated and compared to plain glassy carbon cloth without catalyst (CC ) and platinum containing carbon powder catalyst ( PtC ) in H-type MFCs. Surface extension by carbon aerogel (CA ) enhanced the maximum power density by 34 % compared to CC, to 14.1 W m−3. With nitrogen doped carbon aerogel (NCA) the performance was further increased to 15.7 W m−3. Co-doping the resorcinol-melamine-formaldehyde based aerogel with graphene oxide (GNCA) resulted in an additional power increase of 70 %, indicating that the electrocatalytic activity of NCAs can be considerably improved by co-doping with graphene oxide. Although the performance of GNCA remained below that of PtC (50.2 W m−3) in our investigations, it can be concluded that GNCA based coatings may provide a noble metal free, and therefore competitive and sustainable alternatives for cathode catalysis in MFC based technologies.
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Lee, Eun-Gyung, Daniel Kuppers, Megan Horn, Jacqueline Roy, Cynthia May, and Maxine L. Linial. "A Premature Termination Codon Mutation at the C Terminus of Foamy Virus Gag Downregulates the Levels of Spliced pol mRNA." Journal of Virology 82, no. 4 (December 5, 2007): 1656–64. http://dx.doi.org/10.1128/jvi.00990-07.
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ABSTRACT Foamy viruses (FV) comprise a subfamily of retroviruses. Orthoretroviruses, such as human immunodeficiency virus type 1, synthesize Gag and Pol from unspliced genomic RNA. However, FV Pol is expressed from a spliced mRNA independently of Gag. FV pol splicing uses a 3′ splice site located at the 3′ end of gag, resulting in a shared exon between gag and pol. Previously, our laboratory showed that C-terminal Gag premature termination codon (PTC) mutations in the 3′ shared exon led to greatly decreased levels of Pol protein (C. R. Stenbak and M. L. Linial, J. Virol. 78:9423-9430, 2004). To further characterize these mutants, we quantitated the levels of unspliced gag and spliced pol mRNAs using a real-time PCR assay. In some of the PTC mutants, the levels of spliced pol mRNA were reduced as much as 30-fold, whereas levels of unspliced gag RNA were not affected. Substitutions of a missense codon in place of a PTC restored normal levels of spliced pol mRNA. Disrupting Upf proteins involved in nonsense-mediated mRNA decay (NMD) did not affect Pol protein expression. Introduction of an exonic splicing enhancer downstream of the PTC mutation restored pol splicing to the wild-type level. Taken together, our results show that the PTC mutation itself is responsible for decreased levels of pol mRNA but that mechanisms other than NMD might be involved in downregulating Pol expression. The results also suggest that normal pol splicing utilizes a suboptimal splice site seen for other spliced mRNAs in most retroviruses, in that introduced exonic enhancer elements can increase splicing efficiency.
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Zhu, Jingqiang. "A new combination therapy using recombinant human adenovirus p53 injection (rAd-p53) to manage advanced thyroid cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e17585-e17585. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e17585.
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e17585 Background: Although most thyroid cancers have good clinical outcomes, there still have some advanced and radioiodine-resistant thyroid cancers being lack of effective treatment. In this study, we reported a new combination therapy including recombinant adenovirus-p53 (rAd-p53) to treat advanced thyroid cancers. Methods: Two types of unresectable cancers (one advanced PTC and one ATC) received preoperative intratumoral injection of rAd-p53 combined with radiotherapy to shrink the tumor and surgery to remove the tumor. In the matched controlled clinical trial, 82 advanced PTC patients accorded with the inclusive criteria and exclusion criteria were included and matched into experimental group (EG, n = 41) and control group (CG, n = 41). Compared CG received surgery only, EG received preoperative intratumoral injection of 2×1012rAd-p53 viral particles (VP) per 3 days for 5 times and surgery. Results: In the advanced PTC case, the combination treatments including rAd-p53 gene therapy combined with radiotherapy evidently shrunk the tumor and improved the operative condition. Finally, the patient received a successful surgery to remove the tumor totally. In the ATC case, rAd-p53combined radiotherapy obvious relieved enlargement of the lump in the neck and shrunk the tumor. More importantly, the program of surgery to excise the tumor was deemed suitable for this ATC patient through a series of treatments and severity evaluation. In the matched controlled clinical study, compared the control group (CG), rAd-p53 significantly increased the radically operative rate in experiment group (EG) (92.7% vs73.2 %, P= 0.021, n = 41). The 7 years follow-up data showed rAd-p53 decreased locoregional recurrence rate (19.51% vs 36.59%) and new metastasis rate (7.32% vs 17.07%) and increased the median time to locoregional recurrence (24.5 M vs 23.27 M) and new metastasis (19.0 M vs 9.2 M) and the disease-free survival rate (75.61% vs 46.34%) for patients in EG. Conclusions: The combination therapy improved the prognosis to patients with advanced thyroid cancer, indicating this combination therapy including rAd-p53 has an important implication for managing advanced thyroid cancer.
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Garavelo, Shérrira M., Maria de Lourdes Higuchi, Jaqueline J. Pereira, Marcia M. Reis, Joyce T. Kawakami, Renata N. Ikegami, Suely A. P. Palomino, Nilsa S. Y. Wadt, and Abdelali Agouni. "Comparison of the Protective Effects of Individual Components of Particulatedtrans-Sialidase (PTCTS), PTC and TS, against High Cholesterol Diet-Induced Atherosclerosis in Rabbits." BioMed Research International 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/7212985.
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Previous studies showed the presence ofMycoplasma pneumoniae(M. pneumoniae) and membrane-shed microparticles (MPs) in vulnerable atherosclerotic plaques. H&S Science and Biotechnology developed PTCTS, composed by natural particles from medicinal plants (PTC) combined withtrans-Sialidase (TS), to combat MPs andMycoplasma pneumoniae. Our aim was to determine the effects of the different components of PTCTS in a rabbit model of atherosclerosis. Rabbits were fed with high cholesterol diet for 12 weeks and treated during the last 6 weeks with either vehicle, PTC, TS, or PTCTS. Lipid profile and quantification of MPs positive forMycoplasma pneumoniaeand oxidized LDL antigens were carried out. Aortas and organs were then histologically analyzed. PTCTS reduced circulating MPs positive forMycoplasma pneumoniaeand oxidized LDL antigens, reduced the plaque area in the abdominal aorta, and caused positive remodeling of the ascendant aorta. PTC caused positive remodeling and reduced plaque area in the abdominal aorta; however, TS had a lipid lowering effect. PTCTS components combined were more effective against atherosclerosis than individual components. Our data reinforce the infectious theory of atherosclerosis and underscore the potential role of circulating MPs. Therefore, the removal ofMycoplasma-derived MPs could be a new therapeutic approach in the treatment of atherosclerosis.
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Tam, Benjamin, Dror Sherf, Shira Cohen, Sarah Adi Eisdorfer, Moshe Perez, Adam Soffer, Dan Vilenchik, Sabine Ruth Akabayov, Gerhard Wagner, and Barak Akabayov. "Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis." Chemical Science 10, no. 38 (2019): 8764–67. http://dx.doi.org/10.1039/c9sc02520k.
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Starenki, Dmytro, Nadiya Sosonkina, Seung-Keun Hong, Ricardo V. Lloyd, and Jong-In Park. "Mortalin (GRP75/HSPA9) Promotes Survival and Proliferation of Thyroid Carcinoma Cells." International Journal of Molecular Sciences 20, no. 9 (April 26, 2019): 2069. http://dx.doi.org/10.3390/ijms20092069.
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We previously reported that upregulation of mortalin (HSPA9/GRP75), the mitochondrial HSP70 chaperone, facilitates tumor cell proliferation and survival in human medullary thyroid carcinoma (MTC), proposing mortalin as a novel therapeutic target for MTC. In this report, we show that mortalin is also upregulated in other thyroid tumor types, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and anaplastic thyroid carcinoma (ATC), and that mortalin depletion can effectively induce growth arrest and cell death in human PTC (TPC-1), FTC (FTC133), and ATC (8505C and C643) cells in culture. Intriguingly, mortalin depletion induced varied effects on cell cycle arrest (G0/G1 phase arrest in TPC-1 and C643, G2/M phase arrest in 8505C, and mild G2/M phase arrest with increased sub-G0/G1 population in FTC133) and on the levels of TP53, E2F-1, p21CIP1, p27KIP1, and poly (ADP-ribose) polymerase cleavage in these cells, suggesting that thyroid tumor cells respond to mortalin depletion in a cell type-specific manner. In these cells, we also determined the efficacy of triphenyl-phosphonium-carboxy-proxyl (Mito-CP) because this mitochondria-targeted metabolism interfering agent exhibited similar tumor suppressive effects as mortalin depletion in MTC cells. Indeed, Mito-CP also induced robust caspase-dependent apoptosis in PTC and ATC cell lines in vitro, exhibiting IC50 lower than PLX4032 in 8505C cells and IC50 lower than vandetanib and cabozantinib in TPC-1 cells. Intriguingly, Mito-CP-induced cell death was partially rescued by mortalin overexpression, suggesting that Mito-CP may inactivate a mechanism that requires mortalin function. These findings support the significance of mortalin and mitochondrial activity in a broad spectrum of thyroid cancer.
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Sarközi, Rita, Christine Hauser, Susie-Jane Noppert, Andreas Kronbichler, Markus Pirklbauer, Viktoria Maria Haller, Johannes Grillari, Regina Grillari-Voglauer, Gert Mayer, and Herbert Schramek. "Oncostatin M is a novel inhibitor of TGF-β1-induced matricellular protein expression." American Journal of Physiology-Renal Physiology 301, no. 5 (November 2011): F1014—F1025. http://dx.doi.org/10.1152/ajprenal.00123.2011.
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Matricellular proteins in the kidney have been associated with the development of tubulointerstitial fibrogenesis and the progression of renal disease. This study investigated potential antifibrotic effects of the cytokine oncostatin M (OSM) in human proximal tubule cells (PTC), particularly with regard to inhibition of profibrotic events initiated by TGF-β1. In human PTC, OSM diminished transforming growth factor (TGF)-β1-induced expression of the transcriptional epithelial-mesenchymal transition mediator FoxC2. Furthermore, exposure to OSM attenuated basal and TGF-β1-induced expression of the matricellular proteins SPARC, TSP-1, TNC, and CTGF regardless of the sequence of ligand administration. OSM was shown to result in rapid and sustained phosphorylation of both Stat1 and Stat3 and also in transient phosphorylation of Smad2/3 in contrast to TGF-β1, which demonstrated a gradually building phosphorylation of Smad2/3 and a brief phosphorylation of Smad1/5/8. Utilizing receptor-blocking molecules, we found the inhibitory effect of OSM on TGF-β1-induced CTGF mRNA expression occurs independently of Smad2/3 signaling and present evidence that this effect may be partially driven by OSM receptor-mediated Stat1 and/or Stat3 signaling pathways, thereby providing a mechanism whereby OSM can contribute to tubulointerstitial protection.
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Nalyvaiko, O. I., O. L. Melnikov, L. G. Nalyvaiko, R. V. Petrash, and V. N. Khivrenko. "APPLICATION OF HYDROPHOBIC CEMENT SLURRIES «RAN-M» OF «RAMSINKS-2M» GROUP TO AVOID FLUID KICK." ACADEMIC JOURNAL Series: Industrial Machine Building, Civil Engineering 2, no. 49 (January 28, 2018): 295–300. http://dx.doi.org/10.26906/znp.2017.49.857.
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Laboratory studies of cement slurry and cement stone is established that hydrophobic cement slurry «RAN-M» consists of NTPha additives for well cements PTC-1-100 and «Ramsinks-2M». In the laboratory confirmed the technical parameters of the newest hydrophobic cement slurries (mobility, density, separation, pumpability, etc.) according to the standard requirements in the respective devices. Done such works as: implementation of the selection of formulations of cement slurries with different rate of strength development for different temperature integrals.
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Brodeur, Sheri A., Wayne Huebner, James P. Runt, and Robert E. Newnham. "Phase change materials for thermal stabilization of composite thermistors." Journal of Materials Research 6, no. 1 (January 1991): 175–82. http://dx.doi.org/10.1557/jmr.1991.0175.
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The objective of this investigation was to develop a triphasic PTC thermistor composite which incorporated a phase capable of absorbing heat at a critical temperature, and thus limiting deleterious effects associated with thermal runaway. The system chosen for study was pentaerythritol incorporated into a carbon black–polyethylene thermistor system. Pentaerythritol exhibits a first order tetragonal to cubic phase transition at 185 °C, with a 1.87 to 3.18 J/°C · g change in specific heat and a 425 J/cm3 heat of transition. Composites with room temperature resistivities as low as 0.1 Ω · m, a PTCR effect of up to six orders of magnitude, and reproducible temperature-cycling behavior were developed. The pentaerythritol introduced thermal delays up to 7 min at 185 °C and substantially increased the electrical and mechanical stability of the composites with temperature and voltage cycling. High fields imparted irreversible effects in these composites as reflected by an increase in the room temperature and high temperature resistivity.
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Massé, Astrid, Ruth L. Airs, Brendan J. Keely, and Rutger de Wit. "The impact of different intensities of green light on the bacteriochlorophyll homologue composition of the chlorobiaceae Prosthecochloris aestuarii and Chlorobium phaeobacteroides." Microbiology 150, no. 8 (August 1, 2004): 2555–64. http://dx.doi.org/10.1099/mic.0.27048-0.
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Members of the Chlorobiaceae and Chloroflexaceae are unique among the phototrophic micro-organisms in having a remarkably rich chlorophyll pigment diversity. The physiological regulation of this diversity and its ecological implications are still enigmatic. The bacteriochlorophyll composition of the chlorobiaceae Prosthecochloris aestuarii strain CE 2404 and Chlorobium phaeobacteroides strain UdG 6030 was therefore studied by both HPLC with photodiode array (PDA) detection and liquid chromatography-mass spectrometry (LC-MS). These strains were grown in liquid cultures under green light (480–615 nm) at different light intensities (0·2–55·7 μmol photons m−2 s−1), simulating the irradiance regime at different depths of the water column of deep lakes. The specific growth rates of Ptc. aestuarii under green light achieved a maximum of 0·06 h−1 at light intensities exceeding 6 μmol photons m−2 s−1, lower than the maximum observed under white light (approx. 0·1 h−1). The maximal growth rates of Chl. phaeobacteroides under green light were slightly higher (0·07 h−1) than observed for Ptc. aestuarii and were achieved at 3·5 and 4·3 μmol photons m−2 s−1. LC-MS/MS analysis of pigment extracts revealed most (>90 %) BChl c homologues of Ptc. aestuarii to be esterified with farnesol. The homologues differed in mass by multiples of 14 Da, reflecting different alkyl subsituents at positions C-8 and C-12 on the tetrapyrrole macrocycle. The relative proportions of the individual homologues varied only slightly among different light intensities. The specific content of BChl c was maximal at 3–5 μmol photons m−2 s−1 [400±150 nmol BChl c (mg protein)−1]. In the case of Chl. phaeobacteroides, the specific content of BChl e was maximal at 4·3 μmol photons m−2 s−1 [115 nmol BChl e (mg protein)−1], and this species was characterized by high carotenoid (isorenieratene) contents. The major BChl e forms were esterified with a range of isoprenoid and straight-chain alcohols. The major isoprenoid alcohols comprised mainly farnesol and to a lesser extent geranylgeraniol. The straight-chain alcohols included C15, C15 : 1, C16, C16 : 1 and C17. Interestingly, the proportion of straight alkyl chains over isoprenoid esterified side chains shifted markedly with increasing light intensity: the isoprenoid side chains dominated at low light intensities, while the straight-chain alkyl substituents dominated at higher light intensities. The authors propose that this phenomenon may be explained as a result of changing availability of reducing power, i.e. the highly reduced straight-chain alcohols have a higher biosynthetic demand for NADPH2 than the polyunsaturated isoprenoid with the same number of carbon atoms.
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Gerhardt, Louisa M. S., Jing Liu, Kari Koppitch, Pietro E. Cippà, and Andrew P. McMahon. "Single-nuclear transcriptomics reveals diversity of proximal tubule cell states in a dynamic response to acute kidney injury." Proceedings of the National Academy of Sciences 118, no. 27 (June 28, 2021): e2026684118. http://dx.doi.org/10.1073/pnas.2026684118.
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Acute kidney injury (AKI), commonly caused by ischemia, sepsis, or nephrotoxic insult, is associated with increased mortality and a heightened risk of chronic kidney disease (CKD). AKI results in the dysfunction or death of proximal tubule cells (PTCs), triggering a poorly understood autologous cellular repair program. Defective repair associates with a long-term transition to CKD. We performed a mild-to-moderate ischemia–reperfusion injury (IRI) to model injury responses reflective of kidney injury in a variety of clinical settings, including kidney transplant surgery. Single-nucleus RNA sequencing of genetically labeled injured PTCs at 7-d (“early”) and 28-d (“late”) time points post-IRI identified specific gene and pathway activity in the injury–repair transition. In particular, we identified Vcam1+/Ccl2+ PTCs at a late injury stage distinguished by marked activation of NF-κB–, TNF-, and AP-1–signaling pathways. This population of PTCs showed features of a senescence-associated secretory phenotype but did not exhibit G2/M cell cycle arrest, distinct from other reports of maladaptive PTCs following kidney injury. Fate-mapping experiments identified spatially and temporally distinct origins for these cells. At the cortico-medullary boundary (CMB), where injury initiates, the majority of Vcam1+/Ccl2+ PTCs arose from early replicating PTCs. In contrast, in cortical regions, only a subset of Vcam1+/Ccl2+ PTCs could be traced to early repairing cells, suggesting late-arising sites of secondary PTC injury. Together, these data indicate even moderate IRI is associated with a lasting injury, which spreads from the CMB to cortical regions. Remaining failed-repair PTCs are likely triggers for chronic disease progression.
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Crowe-McAuliffe, Caillan, Michael Graf, Paul Huter, Hiraku Takada, Maha Abdelshahid, Jiří Nováček, Victoriia Murina, Gemma C. Atkinson, Vasili Hauryliuk, and Daniel N. Wilson. "Structural basis for antibiotic resistance mediated by the Bacillus subtilis ABCF ATPase VmlR." Proceedings of the National Academy of Sciences 115, no. 36 (August 20, 2018): 8978–83. http://dx.doi.org/10.1073/pnas.1808535115.
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Many Gram-positive pathogenic bacteria employ ribosomal protection proteins (RPPs) to confer resistance to clinically important antibiotics. In Bacillus subtilis, the RPP VmlR confers resistance to lincomycin (Lnc) and the streptogramin A (SA) antibiotic virginiamycin M (VgM). VmlR is an ATP-binding cassette (ABC) protein of the F type, which, like other antibiotic resistance (ARE) ABCF proteins, is thought to bind to antibiotic-stalled ribosomes and promote dissociation of the drug from its binding site. To investigate the molecular mechanism by which VmlR confers antibiotic resistance, we have determined a cryo-electron microscopy (cryo-EM) structure of an ATPase-deficient B. subtilis VmlR-EQ2 mutant in complex with a B. subtilis ErmDL-stalled ribosomal complex (SRC). The structure reveals that VmlR binds within the E site of the ribosome, with the antibiotic resistance domain (ARD) reaching into the peptidyltransferase center (PTC) of the ribosome and a C-terminal extension (CTE) making contact with the small subunit (SSU). To access the PTC, VmlR induces a conformational change in the P-site tRNA, shifting the acceptor arm out of the PTC and relocating the CCA end of the P-site tRNA toward the A site. Together with microbiological analyses, our study indicates that VmlR allosterically dissociates the drug from its ribosomal binding site and exhibits specificity to dislodge VgM, Lnc, and the pleuromutilin tiamulin (Tia), but not chloramphenicol (Cam), linezolid (Lnz), nor the macrolide erythromycin (Ery).
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Baitsar, Andriy, and Pavlo Horishnyy. "HIGH MOUNTAINS OF THE UKRAINIAN CARPATHIANS: STATE AND PROBLEMS OF CONCEPTS AND TERMINOLOGY." PROBLEMS OF GEOMORPHOLOGY AND PALEOGEOGRAPHY OF THE UKRANIAN CARPATHIANS AND ADJACENT AREAS, no. 14 (December 30, 2022): 5–18. http://dx.doi.org/10.30970/gpc.2022.1.3818.
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The problems of misreading and use of the term "high mountains" in science are considered. Under the conceptual and terminological apparatus is understood the scientific language of a particular field of knowledge. Instead of the term conceptual and terminological apparatus as equivalent use terminology, understanding them as a set of terms of a particular field of science, technology, or art, associated with the relevant system of concepts. The problem of terminology has occupied and continues to occupy an important place in geographical science, in particular in landscape science. Much of the terms and concepts are not always used successfully and expediently in a given context. Landscape science operates with a powerful terminological apparatus, which is constantly improving and evolving. On the example of the Ukrainian Carpathians, possible ways of organizing the conceptual apparatus, its optimal application for the description of high-altitude PTCs are proposed. The high mountains of the Ukrainian Carpathians are mountain PTC (high-altitude areas: peneplenized alpine-subalpine high mountains, ancient glacial-erosive subalpine high mountains) that rise above the natural upper limit of the forest (1240–2061 m; represented by peneplen and forms of Pleistocene glaciation; covered with alpine-subalpine vegetation on mountain-meadow-brown soil and mountain-peat-brown soils. This is a cold climate zone, which is divided into two subzones: colder and less cold. Colder subzone (from 1500 to 2000 m above sea level) is characterized by the sum of active temperatures less than 600° С, hydrothermal coefficient exceeds 5. Less cold subzone is limited by isolines of sums of temperatures 600–1000° С, and also hydrothermal coefficient respectively 5 and 4 (altitude 1250–1500 m asl). Scientific approaches in the study of alpine PTC are considered. The advantages of the landscape approach in the study of high mountains are presented. There is a false statement about the imaginary identity of objects of biogeocenology, ecology and landscape science. Solntsev M. (1967), Isachenko A. (1980) in their works showed the erroneousness of these views. The concept of biocenosis was first introduced by V. Sukachev in 1964. In its classical formulation it is a system of biocenosis and ecotope to which the microclimate in interaction with soil and lithology belongs. Thus, the main feature of the concept of biogeocenosis is that, in addition to the relationship between the biocenter of the system and the elements of the natural environment, there is a relationship between these elements. This allows the biogeocenologist to trace a slightly different path in the study of the high mountains. Changes in microclimatic features in the forest biocenosis can cause deviations in the water regime of the soil, which will weaken the stability of root systems and lead to the formation of windbreaks, windbreaks, dryness and other processes. The landscape approach provides an effective comprehensive assessment of the natural conditions of the territory. The concept of natural territorial complex put forward as a result of formation of landscape science gives the chance to study any natural phenomenon in system of direct and inverse interrelations between equal, though not equivalent components of PTC where the bioelement is taken to level of other elements of systems. In this article we want to address the problems of misreading and use of the term "high mountains" in natural science, on the example of the Ukrainian Carpathians. Keywords: foresttimber – line (TL); polonynas; high mountains; mountain range; Ukrainian Carpathians.
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Muhammad, Umar Abubakar, Lik Gin Tham, Natarajan Perumal, Hassan Mohd Daud, Nur Adeela Yasid, and Mohd Yunus Shukor. "Assessment of acetylcholinesterase (AChE) from Oreochromis mossambicus (Cuvier, 1831) as a source of enzyme for insecticides detection." Bioremediation Science and Technology Research 4, no. 2 (December 31, 2016): 11–17. http://dx.doi.org/10.54987/bstr.v4i2.370.
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In this work we assess the potential of acetylcholinesterase (AChE) from Oreochromis mossambicus (Toman) as a sensitive test for the presence of insecticides. The partial purification and characterization of a soluble AChE from Oreochromis mossambicus brain tissues using affinity chromatography gel (procainamide–Sephacryl S-1000) showed that the partially purified AChE was most active on acetylthiocholine (ATC) but had low activities on propionylthiocholine (PTC) and butyrylthiocholine (BTC), indicating that the partially purified fraction was predominantly AChE. Soluble AChE was partially purified 9.27-fold with a 91.12% yield. The partially purified AChE displayed the highest activity on ATC at pH 7 and at 30oC using 0.1 M Tris buffer. The enzyme exhibited Michaelis-Menten kinetic constants, Km, for ATC, BTC and PTC at 36, 77 and 250 µM, respectively, and the maximum velocities, Vmax, were 18.75, 0.12 and 0.05 µmol/min/mg protein, respectively. Moreover, the AChE from Oreochromis mossambicus presented comparable sensitivity to carbamates and organophosphates insecticides than that from Electrophorus electricus and many other fish AChE by comparing half maximal inhibitory concentration values. Therefore, the enzyme is a valuable source for insecticides detection in Malaysian waters at lower cost.
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Hicks, Hannah M., Veronica L. Espinoza, Sharon B. Sams, Nikita Pozdeyev, and Rebecca E. Schweppe. "Abstract 2434: The role of a more invasive phenotype in response to MAPK-directed therapies in thyroid cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2434. http://dx.doi.org/10.1158/1538-7445.am2022-2434.
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Abstract Advanced papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) are the leading causes of endocrine cancer death. Mutations in the MAP kinase (MAPK) pathway are common in PTC and ATC, especially in BRAF, with a prevalence of 40-60%. Despite the importance of the MAPK pathway in thyroid cancer, therapies targeting this pathway are not approved for BRAF-mutant PTC patients. While the combination of BRAF and MEK inhibition is approved for patients with BRAF-mutant ATC, these patients often progress. An emerging mechanism of resistance to targeted therapies is an invasive phenotype switch in which cells transition from a proliferative, therapy sensitive population to an invasive, therapy resistant population. Here, we sought to determine whether increased invasion plays a role in resistance to BRAFi in BRAF-mutant PTC and ATC. In our panel of BRAF-mutant PTC and ATC cell lines with varying sensitivity/resistance to the BRAF inhibitor dabrafenib (BRAFi), we showed that cells resistant to BRAFi exhibit a 1.8 to 2.2 fold increase (p<0.04) in invasion while sensitive cells do not. Using Reverse Phase Protein Array, we identified a 2.0-fold increase in the extracellular matrix protein, fibronectin (FN1), in response to BRAFi treatment. We further identified a 1.6 to 3.2 fold increase (p<0.02) in FN1 secretion in resistant cell lines and found that conditioned media from BRAFi-treated resistant cells promotes invasion 3.8 to 5.7-fold (p<0.0048). Accordingly, treatment with FN1 phenocopies BRAFi-treatment by increasing invasion 1.9 to 2.1 fold (p<0.04), and depletion of FN1 blocks this increase in invasion. Resistant cells with depleted FN1 also fail to exhibit a BRAFi-induced increase in secreted FN1. MAPK pathway reactivation is a common mechanism of resistance to inhibitors of the MAPK pathway, which we have shown can be blocked by dual BRAF and ERK inhibition (Hicks, HM; McKenna, LR et al. Mol Carcinog. 60(3) 2021). ERK inhibition also mitigates the increase in invasion observed in response to single-agent BRAFi (p<0.0014) or FN1 (p<0.0271) in resistant cells. We further observed that dual inhibition of BRAF and ERK slows tumor growth in vivo in a BRAFi-resistant patient-derived xenograft model (p=0.02). These data indicate that thyroid cancer cells resistant to BRAF inhibition exhibit a more invasive phenotype characterized by an increase in FN1 and a pro-invasive secretome. Dual inhibition of BRAF and ERK ablates this BRAFi-driven increase in invasion and slows tumor growth in vivo, providing a potential therapeutic strategy for BRAF-mutant thyroid cancer patients. Citation Format: Hannah M. Hicks, Veronica L. Espinoza, Sharon B. Sams, Nikita Pozdeyev, Rebecca E. Schweppe. The role of a more invasive phenotype in response to MAPK-directed therapies in thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2434.
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Garagiola, Isabella, Silvia Lavoretano, Hale Oren, Martina Bohm, Pier Mannuccio Mannucci, and Flora Peyvandi. "Non-Sense-Mediated mRNA Decay in ADAMTS13 Gene Caused by 29 Nucleotide Deletion." Blood 108, no. 11 (November 16, 2006): 1061. http://dx.doi.org/10.1182/blood.v108.11.1061.1061.
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Abstract Genetic or acquired deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP), a condition characterized by thrombocytopenia and hemolytic anemia with microvascular platelet thrombi. Several mutations spread across the ADAMTS13 gene have been identified in patients with congenital TTP. We analyzed the ADAMTS13 gene in two Turkish brothers affected by hereditary TTP. One of them is a 23 years old male, who experienced two acute TTP episodes and is currently in prophylactic treatment with plasma infusion once a month. His sister has mild thrombocytopenia and a mild hemolytic anemia but never had any acute TTP episode.Their ADAMTS13 antigen level and activity in plasma were found to be <1% and <6% respectively. Genetic analysis revealed that both patients are double heterozygote for a 29 nucleotide deletion in exon 3 (291–319del) leading to a premature stop at codon 368 in the metalloprotease domain (Peyvandi,2004) and a single base insertion in exon 29 (4143–4144insA) in the second CUB domain resulting in the loss of the 49 amino acids (Schneppenheim,2003). To evaluate the molecular mechanism of these mutations, we cloned the ADAMTS13 cDNA into pcDNA3.1 expression vector and introduced each mutation using the wild type cDNA as template (pcDNA3.1ADAMTS13insA and pcDNA3.1ADAMTS13–29del). These constructs were transiently transfected in HEK-293 cells. Expression studies demonstrated that the 4143–4144insA mutation leads to a secretion defect resulting in a reduced protease activity, measured by CBA in cell supernatant (14% of wild type activity), as reported by Pimanda (2004).The intracellular accumulation was demonstrated by WB analysis and confirmed by immunofluorescence studies showing that rADAMTS13insA was present throughout the cytoplasm while the rADAMTS13WT was mainly localized in the perinuclear area.Expression studies of 29bp deletion showed the absence of recombinant protein in cell supernatant analyzed by WB. Previous studies showed that in mammalian cells exists a regulatory mechanism (PTC-mediated decay mechanism) that triggers the destruction of PTC-bearing mRNAs and a reduction in m-RNA levels, and this decay mechanism is intron-dependent (Zhang, 1998). The 29bp deletion leads to PTC in the metalloprotease domain. To verify whether the PTC introduced by 29bp deletion could lead to degradation and decrease of mRNA level, we have constructed a minigene extending from exon 4 to exon 6 of ADAMTS13 gene including introns 4 and 5. Subsequently this fragment was subcloned in frame into pcDNA3.1ADAMTS13–29del expression vector. Reverse transcription PCR was performed on total mRNA isolated from cells transfected with ADAMTS13-WT and ADAMTS13–29del constructs.The band obtained by RT-PCR of ADAMTS13–29del mRNA was fainter than that ADAMTS13WT (roughly 10%) suggesting that the presence of PTC due to the 29bp deletion triggers probably a decay process leading to a reduction of ADAMTS13 mRNA level. In conclusion, our work shows how the association of two different ADAMTS13 gene mutations could lead to a severe ADAMTS13 deficiency, with effects on two different levels: a partial impairment of mRNA synthesis due to 29bp deletion, and an alteration of the secretion pathway caused by 4143–4144insA.
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Li, Chenggong, Qi Chang, Jing Wang, Mengyi Du, Lin Liu, Haiming Kou, Cong Lu, et al. "Novel CD19-Specific γ/δ TCR-T Cells in Relapsed or Refractory Diffuse Large B-Cell Lymphoma." Blood 138, Supplement 1 (November 5, 2021): 826. http://dx.doi.org/10.1182/blood-2021-152661.
Full textAbstract:
Abstract Background: T cell receptor(TCR)-engineered T cell therapy, by replacing the antigen recognition domain of TCR with an antibody-derived Fab fragment, is another active field of cellular immunotherapy for cancer. We previously developed a human anti-CD19 antibody (ET190L1), and found that ET190L1-TCR-T cells maintained comparable anti-tumor potency with less cytokine release to CD28-costimulated ET190L1-CAR and CD137-based CTL019 T cells (Cell Discov. 2018 Nov 20;4:62.). ET019003-T cells are novel anti-CD19 γδ TCR-T cells generated based on ET190L1-TCR-T cells by adding an independent chimeric signaling receptor(CSR) to further promote T cell activation and reduce cytokine release (Figure 1A). We report outcomes for adult patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) treated with ET019003-T cells. Methods: Our first-in-human, single-center, phase 1 study (NCT04014894) was designed to evaluate the safety and efficacy of ET019003-T cells in patients with CD19 + malignancies, of whom 8 with RR DLBCL are reported here. Eligible patients must have (1) histologically confirmed DLBCL; (2) CD19 + on malignant cells by IHC; (3) refractory disease as defined in the SCHOLAR-1 study, or recurrent disease within 6 months or at least 2 times after CR; (4) prior therapy including an anti-CD20 monoclonal antibody and an anthracycline. Patients with CNS lymphoma were eligible. Bridging therapy wasn't allowed after apheresis. Cyclophosphamide 250 mg/m 2 on day -5 and fludarabine 25 mg/m 2 on day -5 to -3 were used as the conditioning regimen. Planned dose levels were 2, 4x10 6 TCR+T cells/kg, and repeated infusions were allowed. Primary objectives were incidence of adverse events (AEs) and overall response rate(ORR). CRS and neurotoxicity were graded using the ASTCT criteria, and other AEs using CTCAE v5.0. Response was assessed per Lugano Criteria (Cheson 2014). Results: 8 pts (median age 50, range 33-71) received infusion of ET019003-T cells (6 at 2x10 6/kg, and 2 at 4x10 6/kg) and were included in the study analysis. Patient enrollment was ceased in June, 2020. Pt1 had primary CNS lymphoma, and 62.5% had stage 4 disease against Ann Arbor staging. MYC/BCL2/BCL6 triple expression was detected in 50% of pts, and double expression in 25%. Pts had received a median of 4.5 (range 2-8) prior lines of treatment, and 37.5% received prior PD-1 inhibitors, and 62.5% had primary refractory disease. 3 pts (37.5%) experienced grade 1 CRS that resolved spontaneously; 1(pt2) developed grade 3 neurotoxicity (dose-limiting toxicity), manifested by confusion, barylalia, tremor and agitation, which occurred after CRS and responded to corticosteroids. The most common AE was neutropenia (100%), and 62.5% were related to conditioning regimen; other hematologic AEs included thrombocytopenia (37.5%) and anemia (12.5%). Pt8 had pulmonary infection on day 15, and pt1 experienced viral encephalitis at 18 months, and both were manageable. As of July 20, 2021, median follow-up after infusion was 15 months (range 2-24.7). 6 pts(75%) achieved a clinical response, and 5(62.5%) reached CR, of whom 80% kept ongoing CR (all at 18+ months). 3 pts received a second infusion, pt5 for consolidation therapy after CR, and pt2 and pt7 for salvage therapy after disease progression, but response wasn't observed (Figure 1B). Pt1 with primary CNS lymphoma got continuing CR, without CRS or neurotoxicity (Figure 1C). The rate of overall survival, progression-free survival, and duration of response at 12 months was 87.5%, 62.5% and 66.7%, respectively. ET019003 cells showed striking peak expansion during 10-20 days post infusion as measured as ET019003+ cells per milliliter of PB by flow cytometry and copies per microgram of genomic DNA by qPCR, but poor expansion was observed in the second infusions (Figure 1D). ET019003 cells were detectable in cerebrospinal fluid of pt1, and continued to be detectable at 12+ months in PB of pt3 and pt5. Serum cytokine levels increased mildly post-infusion, except elevated IL-6 (>10 folds of upper limit of normal) in 3 pts (pt1 with a high baseline level, coinciding with onset of CRS and neurotoxicity of pt2, and concurrent with pulmonary infection of pt8). Conclusion: These data suggest ET019003-T cells had a good safety profile and could induce durable remission in patients with RR DLBCL, even with primary CNS lymphoma. γ/δ TCR-T cells may present a potential therapeutic option for these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.