Molecular breakdown: a comprehensive view of anaplastic lymphoma kinase (<i>ALK</i>)<i>‐</i>rearranged non‐small cell lung cancer

Noh, Ka‐,Won,Lee, Mi‐,Sook,Lee, Seung Eun,Song, Ji‐,Young,Shin, Hyun‐,Tae,Kim, Yu Jin,Oh, Doo Yi,Jung, Kyungsoo,Sung, Minjung,Kim, Mingi,An, Sungbin,Han, Joungho,Shim, Young Mo Longman 2017 The Journal of pathology Vol.243 No.3

<P><B>Abstract</B></P><P>Most anaplastic lymphoma kinase (<I>ALK</I>)‐rearranged non‐small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some <I>ALK</I>‐rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of <I>ALK</I> fusions in small cohorts, or were conducted <I>in vitro</I> and/or <I>in vivo</I> to investigate the function of ALK. One of the suggested theories describes how echinoderm microtubule‐associated protein‐like 4 (<I>EML4</I>)<I>–ALK</I> variants play a role towards different sensitivities in ALK inhibitors. Until now, there has been no integrated comprehensive study that dissects <I>ALK</I> at the molecular level in a large scale. Here, we report the largest extensive molecular analysis of 158 <I>ALK</I>‐rearranged NSCLCs and have investigated these findings in a cell line construct experiment. We discovered that NSCLCs with <I>EML4–ALK</I> short forms (variant 3/others) had more advanced stage and frequent metastases than cases with the long forms (variant 1/others) (<I>p</I> = 0.057, <I>p</I> < 0.05). <I>In vitro</I> experiments revealed that <I>EML4–ALK</I> short forms show lower sensitivity to ALK inhibitors than do long forms. Clinical analysis also showed a trend for the short forms showing worse PFS. Interestingly, we found that breakpoints of <I>ALK</I> are evenly distributed mainly in intron 19 and almost all of them undergo a non‐homologous end‐joining repair to generate <I>ALK</I> fusions. We also discovered four novel somatic <I>ALK</I> mutations in NSCLC (T1151R, R1192P, A1280V, and L1535Q) that confer primary resistance; all of them showed strong resistance to ALK inhibitors, as G1202R does. Through targeted deep sequencing, we discovered three novel <I>ALK</I> fusion partners (<I>GCC2</I>, <I>LMO7</I>, and <I>PHACTR1</I>), and different <I>ALK</I> fusion partners showed different intracellular localization. With our findings that the <I>EML4–ALK</I> variants, new <I>ALK</I> somatic mutations, and novel <I>ALK</I>‐fusion partners may affect sensitivity to ALK inhibitors, we stress the importance of targeted therapy to take the <I>ALK</I> molecular profiling into consideration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>

Effect of dietary zinc proteinate supplementation on growth performance, and skin and meat quality of male and female broiler chicks.

Salim, H M,Lee, H R,Jo, C,Lee, S K,Lee, B D Longman 2012 British poultry science Vol.53 No.1

<P>1. An experiment was conducted to evaluate the effect of dietary zinc proteinate (ZP) supplementation on growth performance and on skin and meat quality of male and female broiler chicks. 2. A total of 240 1-d-old male and 240 1-d-old female broiler chicks were randomly distributed into 24 floor pens (12 replicate pens/sex; 20 birds/pen) and were given either 0 (Control diet) or 40?mg/kg ZP (ZP 40), resulting in a 2??2 factorial arrangement of treatments. 3. The growth performance of male and female broiler chicks was not affected by the ZP supplementation, but the males showed significantly higher growth performance than did females. 4. ZP supplementation increased the total thickness of skin in both sexes, and males had thicker skin than females. It also increased the collagen content of skin, but not that of meat. Males had higher skin collagen contents than did females, but no sex difference was found in the meat collagen contents. 5. ZP supplementation did not affect the shear force values of skin and meat; however, males had higher shear force values of back skin than females. ZP supplementation increased the zinc contents of thigh meat and plasma in both sexes. Males had higher zinc contents in back skin than females. 6. It is concluded that dietary ZP supplementation could increase the skin quality of broiler chicks in both sexes, particularly in female broilers, without any effect on growth performance. Male broilers have better growth performance and skin quality than females.</P>

Supplementation of graded levels of organic zinc in the diets of female broilers: effects on performance and carcase quality.

Salim, H M,Lee, H R,Jo, C,Lee, S K,Lee, B D Longman 2011 British poultry science Vol.52 No.5

<P>Zinc is an essential trace element. The objective of this research was to investigate the effects of various levels of organic zinc (OZ) supplementation on growth performance and carcase quality of female broiler chickens. A total of 3200 1-d-old female broiler chicks were randomly allotted to 16 floor pens with 200 birds per pen. A maize-wheat-soyabean meal basal diet (Control) was formulated and 20 mg/kg OZ (20 OZ), 40 mg/kg OZ (40 OZ), and 80 mg/kg OZ (80 OZ) were added to the basal diet to form 4 dietary treatments with 4 replicates per treatment. The OZ source was zinc proteinate which contained 15% zinc. Results showed no significant difference between the treatments in growth performance. A significant increase in thigh skin epidermis and dermis thickness was shown in the OZ supplementation groups; however, no effect was found on the thickness of back skin epidermis and dermis. Collagen contents in breast and thigh meats were not influenced by OZ supplementation but a significant increase in collagen content was found in the back and thigh skin. This increase in collagen content was significantly greater in the back and thigh skin of OZ 80 than with OZ 20. Shear force value and zinc concentration in skins and meat were not significantly influenced by supplementation with OZ. It is concluded that dietary OZ does not improve growth performance of broilers; however, it could increase skin thickness by increasing collagen content in skin, thereby improving carcase quality.</P>

Variants of A Not-A and 2AFC tests: Signal Detection Theory models

Hautus, M.J.,van Hout, D.,Lee, H.S. Longman Scientific Technical ; Elsevier Science Pu 2009 Food quality and preference Vol.20 No.3

Signal Detection Theory provides an approach to modelling difference test procedures that allows an estimate of the sensory difference between products to be obtained independently of the response bias and decision strategy used by the judge, and of the test procedure used to estimate that difference. The estimate of sensory difference obtained, d', is therefore much closer to a 'true' estimate of sensory difference than many other measures employed by sensory scientists. The methods used to generate models based on Signal Detection Theory are standard, and these methods are applied to the development of models for two test procedures (A Not-A and 2AFC) and their reminder equivalents (A Not-AR and 2AFCR). 2AFCR is procedurally identical to the duo-trio procedure with a constant reference; however, it is shown that there is more than one decision strategy available to the judge in this task.

Sensory difference tests: Overdispersion and warm-up

Angulo, O.,Lee, H.S.,O'Mahony, M. Longman Scientific Technical ; Elsevier Science Pu 2007 Food quality and preference Vol.18 No.2

For sensory difference tests, one way, but not the only way, of dealing with the problem of overdispersion is to use a beta-binomial analysis. Commonly, binomial statistical analyses are used for these methods and they assume that the sensitivity of the judges is uniform. However, judge sensitivity varies and this adds a problematical extra variance to the distribution. This is termed overdispersion and renders simple binomial analysis prone to Type I error. The distribution of sensitivity of the judges is described by a beta-distribution. The analysis, combining beta and binomial distributions, gives an index, gamma. This ranges from zero, for no overdispersion, to unity, for total overdispersion. A compact beta-distribution clustered around the mean of the binomial distribution, would add little extra variance and elicit minimum distortion of the binomial distribution, yielding a zero or near zero gamma value. A more scattered or even bimodal beta-distribution would have a substantial effect and yield a significant gamma value. One question that has been posed is whether some test methods are more prone to overdispersion than others. Yet, a consideration of the reasons for overdispersion would suggest that significant gamma values were more a result of obtaining a heterogenous sample of sensitive and insensitive judges by chance. To confirm this, 'less sensitive' and 'more sensitive' samples of judges performed 2-AFC and 3-AFC tests with resulting zero gamma values, indicating no overdispersion. However, when the less and more sensitive groups were combined, significant gamma values were obtained, indicating the presence of overdispersion. However, in a further experiment using 2-AFC tests, when the 'less sensitive' group had its sensitivity increased by a 'warm-up' procedure, combination with the 'more sensitive' group did not result in overdispersion.

Effects of interval length between tasting sessions and sweetener level on long-term acceptability of novel green tea drinks

Son, J.S.,Hong, J.H.,Kim, K.O. Longman Scientific Technical ; Elsevier Science Pu 2010 Food quality and preference Vol.21 No.8

The objective of this study was to investigate the effects of the interval length between sessions (1-day vs. 3-day), the sweetener level (Optimal (OP) vs. Low (LO)), and the number of stimuli (one vs. two) on long-term acceptability of a novel green tea drink. Two consumer groups (N=80) rated their liking of two drinks (OP and LO) while another 4 consumer groups (N=162) rated only one drink over 10 sessions at either 1-day or 3-day intervals. Repeated consumption led to an overall increase in liking of the novel drink even though the patterns of increase were different according to the sweetener level and the interval length. Higher sweetener level and shorter interval length might contribute to increase in liking score during the earlier sessions and stable liking during the later sessions for novel green tea drink.

Comparison of performance in the A-Not A, 2-AFC, and same-different tests for the flavor discrimination of margarines: The effect of cognitive decision strategies

Lee, H.S.,van Hout, D.,Hautus, M.J. Longman Scientific Technical ; Elsevier Science Pu 2007 Food quality and preference Vol.18 No.6

The performance of three different discrimination tests (A-Not A, 2-AFC, same-different) was investigated to explore the effects of varying aspects of the test protocols, such as the familiarization procedure and retasting of the reference (A), during testing on discriminability and the cognitive decision strategy used in the tests, when discriminating between the two different margarines. Seven judges, who were not familiar with margarine products, each gave 24 ratings for each of six protocols, resulting in 168 ratings in the pooled data, and from which R-indices and d' estimates were calculated. When both test products were presented beforehand for familiarization, judges adopted the beta cognitive decision strategy. When only the reference (A) was presented to the judges beforehand for familiarization, and the reference (A) was retasted before the test product either by prescription or at will, the tau cognitive decision strategy was adopted. When the number of samples tasted within a test increased, discriminability was considerably decreased. Such differences between test protocols were explained in terms of the concept formation of the test products, carry-over and fatigue effects, and memory problems caused by longer time-intervals between tastings.

Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking

Jeong, Haengdueng,Lim, Kyung‐,Min,Kim, Kwang H,Cho, Yejin,Lee, Buhyun,Knowles, Byron C,Roland, Joseph T,Zwerner, Jeffrey P,Goldenring, James R,Nam, Ki Taek Longman 2019 The Journal of pathology Vol.249 No.2

<P><B>Abstract</B></P><P>Rab25 can function as both a tumor suppressor and a tumor promoter across different tissues. This study sought to clarify the role of Rab25 as a tumor suppressor in skin squamous cell carcinoma (SCC). Rab25 loss was closely associated with neoplastic transition in both humans and mice. Rab25 loss was well correlated with increased cell proliferation and poor differentiation in human SCC. While Rab25 knockout (KO) in mice did not induce spontaneous tumor formation, it did significantly accelerate tumor generation and promote malignant transformation in a mouse two‐stage skin carcinogenesis model. Xenografting of a Rab25‐deficient human keratinocyte cell line, HaCaT, also elicited neoplastic transformation. Notably, Rab25 deficiency led to dysregulation of integrins β1, β4, and α6, which matched well with increased epidermal proliferation and impaired desmosome–tight junction formation. Rab25 deficiency induced impairment of integrin recycling, leading to the improper expression of integrins. In line with this, significant attenuation of integrin β1, β4, and α6 expression was identified in human SCCs where Rab25 was deficient. Collectively, these results suggest that loss of Rab25 promotes the development and neoplastic transition of SCC through dysregulation of integrin trafficking. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>

Serological surveillance studies confirm the Rift Valley fever virus free status in South Korea.

Kim, Hyun Joo,Park, Jee-Yong,Jeoung, Hye-Young,Yeh, Jung-Yong,Cho, Yun-Sang,Choi, Jeong-Soo,Lee, Ji-Youn,Cho, In-Soo,Yoo, Han-Sang Longman Group [etc.] ; Kluwer Academic Publishers 2015 Tropical animal health and production Vol.47 No.7

<P>Rift Valley fever is a mosquito-borne zoonotic disease of domestic ruminants. This disease causes abortions in pregnant animals, and it has a high mortality rate in newborn animals. Recently, a Rift Valley fever virus (RVFV) outbreak in the Arabian Peninsula increased its potential spread to new regions worldwide. In non-endemic or disease-free countries, early detection and surveillance are important for preventing the introduction of RVFV. In this study, a serological surveillance was conducted to detect antibodies against RVFV. A total of 2382 serum samples from goats and cattle were randomly collected from nine areas in South Korea from 2011 to 2013. These samples were tested for antibodies against RVFV, using commercial ELISA kits. None of the goats and cattle were positive for antibodies against RVFV. This finding suggests that this disease is not present in South Korea, and furthermore presents the evidence of the RVFV-free status of this country.</P>

Concurrent elicitation of hedonic and CATA/RATA responses with Chinese and Korean consumers: Hedonic bias is unlikely to occur

Jaeger, S.R.,Kim, K.O.,Lee, S.M.,Hunter, D.C.,Kam, K.,Chheang, S.L.,Jin, D.,Lee, P.Y.,Xia, Y.,Ares, G. Longman Scientific Technical ; Elsevier Science Pu 2017 Food quality and preference Vol.56 No.1

<P>In line with research in non-Western countries becoming main-stream, the need to validate existing research methods with consumers from these populations increase. The present research contributes hereto by quasi-replicating with Korean and Chinese consumers previous research concerning the risk of hedonic product responses being biased by co-elicitation of CATA/RATA questions for sensory product characterisation. Using consumers in several Western countries it was previously reported that bias could occur, but was unlikely to. Eleven studies involving 1000 East Asian consumers confirmed this conclusion. The studies were conducted with diversified populations and across multiple product categories. Across 7 studies, there were no instances where CATA co-elicitation was found to bias hedonic scores. However, in one of four studies where RATA responses were co-elicited bias did occur, and hedonic scores were, on average, lower when RATA responses were co-elicited. It is recommended that the research be replicated with consumers residing in their home countries and extended to other East and South-East Asian counties. (C) 2016 Elsevier Ltd. All rights reserved.</P>