Affiliation to mature B cell repertoire and positive selection can be separated in two distinct processes

Using an 'oligoclonal' model, we have previously shown that mice transgenic for a mu chain (H3) and deficient for kappa chain expression display a mature B cell repertoire largely dominated by the H3/lambda1 pair, while the four H3/lambda available combinations can be observed in the immature B cell compartment. This led us to propose the existence of a positive selection process. To test this hypothesis, we have introduced the SJL lambda locus coding for a defective lambda1 chain (lambda1(s)) that creates a dysfunctional Ig receptor complex during B cell differentiation. Our results show that the lambda1(s) defect impairs the development of mature B cells when the H3-mu transgene insert is present in the hemizygous state. This suggests that the Gly --> Val substitution present in the C(lambda)1(s) chain at position 155 is sufficient to abrogate the selection of the H3/lambda1 pair. Unexpectedly, when the H3-mu transgene array is present in a homozygous state in lambda1(s) mice but not in 'wild-type' lambda1 mice (lambda1(+)), a significant number of mature B cells expressing all H3/lambda combinations can be developed. These results indicate that the overriding H3/lambda1 dominance observed in lambda1(+) mice is due to a positive selection process and not to a negative selection of other H3/lambda combinations. They also show that the export of B cells to the periphery can be controlled by the expression of the mu chain.     

Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation

Neuroinflammation constitutes a normal part of the brain immune response orchestrated by microglial cells. However, a sustained and uncontrolled production of proinflammatory factors together with microglial activation contribute to the onset of a chronic low-grade inflammation, leading to neuronal damage and cognitive as well as behavioral impairments. Hence, limiting brain inflammatory response and improving the resolution of inflammation could be particularly of interest to prevent these alterations. Dietary n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides are good candidates because of their immunomodulatory and proresolutive properties. These compounds are present in a fish hydrolysate derived from marine-derived byproducts. In this study, we compared the effect of an 18-day supplementation with this fish hydrolysate to a supplementation with docosahexaenoic acid (DHA) on lipopolysaccharide (LPS)-induced inflammation in mice. In response to peripherally injected LPS, the fish hydrolysate supplementation decreased the hippocampal mRNA expression of the proinflammatory cytokines IL-6 (p < 0.001), IL-1β (p = 0.0008) and TNF-α (p < 0.0001), whereas the DHA supplementation reduced only the expression of IL-6 (p = 0.004). This decline in proinflammatory cytokine expressions was associated with an increase in the protein expression of IκB (p = 0.014 and p = 0.0054 as compared to the DHA supplementation and control groups, respectively) and to a modulation of microglial activation markers in the hippocampus. The beneficial effects of the fish hydrolysate could be due in part to the switch of the hippocampal oxylipin profile towards a more anti-inflammatory profile as compared to the DHA supplementation. Thus, the valorization of fish byproducts seems very attractive to prevent and counteract neuroinflammation.     

Intravenous Lipid Emulsions in the Prevention and Treatment of Liver Disease in Intestinal Failure

The development of intestinal failure-associated liver disease (IFALD) in pediatric and adult patients on parenteral nutrition is usually multifactorial in nature due to nutritional and non-nutritional causes. The role of lipid therapy as a contributing cause is well-established with the pathophysiological pathways now better understood. The review focuses on risk factors for IFALD development, biological effects of lipids, lipid emulsions and the mechanisms of lipid toxicity observed in laboratory animals followed by a synopsis of clinical studies in pediatric and adult patients. The introduction of fish oil-based lipid emulsions that provide partial or complete lipid replacement therapy has resulted in resolution of IFALD that had been associated with soybean oil-based therapy. Based on case reports and cohort studies in pediatric and adult patients who were at risk or developed overt liver disease, we now have more evidence that an early switch to partial or complete fish oil–based lipid therapy should be implemented in order to successfully halt and reverse IFALD.     

The Joint Effects of Diet and Dietary Supplements in Relation to Obesity and Cardiovascular Disease over a 10-Year Follow-Up: A Longitudinal Study of 69,990 Participants in Australia

It is unknown whether a healthy diet or unhealthy diet combined with specific supplements may jointly contribute to incidence of obesity and cardiovascular disease (CVD). We included 69,990 participants from the 45 and Up Study who completed both baseline (2006–2009) and follow-up (2012–2015) surveys. We found that compared to participants with a long-term healthy diet and no supplement consumption, those with a long-term healthy diet combined with multivitamins and minerals (MVM) or fish oil consumption were associated with a lower incidence of CVD (p < 0.001); whilst those with an unhealthy diet and no MVM or fish oil consumption were associated with a higher risk of obesity (p < 0.05). Compared to participants with a long-term healthy diet and no calcium consumption, the combination of a long-term healthy diet and calcium consumption was linked to a lower risk of CVD (IRR = 0.87, 95% CI: 0.78; 0.96). In conclusion, a long-term healthy diet combined with MVM or fish oil was associated with a lower incidence of CVD. Participants who maintained a healthy diet and used calcium supplements were associated with a lower incidence of obesity. However, these associations were not found among those with an unhealthy diet, despite taking similar supplements.     

高效液相色谱-电感耦合等离子体质谱法测定海鱼中无机砷

目的建立测定海鱼中无机砷含量的高效液相色谱-电感耦合等离子体质谱法。方法海鱼样品经稀硝酸超声热水浴提取后,AS7阴离子交换色谱柱分离,3.5 mmol/L(NH4)2CO3+1%甲醇与100 mmol/L(NH4)2CO3+1%甲醇流动相梯度洗脱,电感耦合等离子体质谱仪测定,以保留时间定性,外标法定量。结果在1~100μg/L的线性范围,6种砷形态化合物的回归方程均呈良好的线性关系,相关系数均优于0.9996,检出限为0.05~0.25μg/L,定量限为0.17~0.84μg/L,3个浓度加标回收率为88.5%~106.4%,相对标准偏差为2.5%~4.9%。结论本方法满足海鱼中无机砷含量的测定要求,提取快速,稳定,操作简单,检出限低,方法的重现性好,灵敏度高。     

Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice

Mice expressing transgenic T cell receptors (TCR) are used to explore important questions in immunity. However, transgene expression may have unexpected effects. We previously reported a B cell immunodeficiency, comprising decreased B cell numbers and diminished antibody responses, in mice that express a transgenic TCR specific for nicotinic acetylcholine receptor; the mice were generated using cassette vectors designed specifically for transgenic TCR expression [see Kouskoff et al. J. Immunol. Methods 1995. 180: 273-280]. We now show data suggesting that this defect is due to the expression and accumulation of TCR alpha and beta chains inside B cells and induction of an endoplasmic reticulum stress response, causing apoptosis at the pre B-I and later B cell stage. Thus, inappropriate transgene expression can profoundly affect B cells, leading to a previously undescribed mechanism of immunodeficiency.     

The influence of positive selection on RAG expression in thymocytes

The expression of recombination activating gene (RAG) products, responsible for T cell receptor (TcR) gene rearrangement, is shut off during positive selection of thymocytes. The precise stage at which this down-regulation occurs remains somewhat controversial. We have analyzed RAG-1 expression in thymocytes of TcR transgenic mice carried on selecting versus non-selecting genetic backgrounds, both by in situ hybridization on thymus sections and by polymerase chain reaction amplification of RNA from sorted cells. The data from several transgenic lines indicate that RAG expression is already reduced in immature, cortical, CD4⁺CD8⁺ cells in the presence of positively selecting major histocompatibility complex molecules, although complete shut-off is not achieved until the mature, medullary, single-positive stage. This finding has practical and theoretical significance for studies on the mechanism of positive selection.     

渤海鱼类和头足类异尖科线虫幼虫感染情况调查

[目的 ]调查渤海鱼类和头足类异尖科线虫幼虫感染情况 .[方法 ]对渤海 2 5种鱼 2 90尾和 3种头足类 10 8尾进行剖检 .[结果 ]发现 19种鱼 15 6尾和 1种头足类 8尾感染异尖科线虫幼虫 6种 ,计73 2 7条 .从 15种鱼 (N =191)中的 12 1尾 ( 63 4 % )和一种头足类 (N =5 4 )中的 8尾 ( 14 8% )体内检出简单异尖线虫幼虫 5 992条 ,占总数的 81 8% ,4种鱼是本幼虫的新发现宿主 .其余 13 3 5条幼虫中 ,15 4( 2 1% )条为鲔蛔线虫B型幼虫 ,采自 4种鱼 2 3尾 ;10 13 ( 13 8% )条为鲔蛔线虫C型幼虫 ,采自 13种鱼79尾 ;164( 2 2 % )条为宫脂线虫中国V型幼虫 ,采自 4种 2 0尾鱼 ;2种鱼感染针蛔虫幼虫 3条 ;仅发现 1条伪新地蛔虫幼虫 .     

转小鼠金属硫蛋白基因集胞藻6803及其野生藻培养

通过摇瓶培养考察转小鼠金属硫蛋白基因集胞藻６８０３及其野生藻的光合自养培养过程中碳源浓度、氮源浓度和光照度对这两种藻生长的影响。野生藻的最适生长碳源浓度（０．０５－０．５ｇ／Ｌ）比转基因藻的最适生长碳源浓度（０．０２－０．０５ｇ／Ｌ）高。氮源浓度对转基因藻和野生藻的影响趋势相同。在０．３－４．５ｇ／Ｌ范围内,随着氮源浓度的增高,藻体生长的最大细胞浓度降低。转基因藻生长的最佳光照度为１５００ｌｘ,野