Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK alpha-dependent noncanonical NF-kappaB activation

Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1)-induced NF-kappaB activation is important for infected cell survival. LMP1 activates NF-kappaB, in part, by engaging tumor necrosis factor (TNF) receptor-associated factors (TRAFs), which also mediate NF-kappaB activation from LTbetaR and CD40. LTbetaR and CD40 activation of p100/NF-kappaB2 is now known to be NIK/IKKalpha-dependent and IKKbeta/IKKgamma independent. In the experiments described here, we found that EBV LMP1 induced p100/NF-kappaB2 processing in human lymphoblasts and HEK293 cells. LMP1-induced p100 processing was NIK/IKKalpha dependent and IKKbeta/IKKgamma independent. Furthermore, the LMP1 TRAF-binding site was required for p100 processing and p52 nuclear localization, whereas the LMP1 death domain-binding site was not. Moreover, the LMP1 TRAF-binding site preferentially caused RelB nuclear accumulation. In murine embryo fibroblasts (MEFs), IKKbeta was essential for LMP1 up-regulation of macrophage inflammatory protein (MIP)-2, TNFalpha, I-TAC, ELC, MIG, and CXCR4 RNAs. Interestingly, in IKKalpha knockout MEFs, LMP1 hyperinduced MIP-2, TNFalpha, and I-TAC expression, consistent with a role for IKKalpha in down-modulating canonical IKKbeta activation or its effects. In contrast, LMP1 failed to up-regulate CXCR4 and MIG RNA in IKKalpha knockout MEFs, indicating a dependence on noncanonical IKKalpha activation. Furthermore, LMP1 up-regulation of MIP-2 RNA in MEFs was both IKKbeta- and IKKgamma-dependent, whereas LMP1 upregulation of MIG and I-TAC RNA was fully IKKgamma independent. Thus, LMP1 induces typical canonical IKKbeta/IKKgamma-dependent, atypical canonical IKKbeta-dependent/IKKgamma-independent, and noncanonical NIK/IKKalpha-dependent NF-kappaB activations; NIK/IKKalpha-dependent NF-kappaB activation is principally mediated by the LMP1 TRAF-binding site.     

阻塞性睡眠呼吸暂停患者快速动眼睡眠期和非快速动眼睡眠期与肺动脉高压的关系

目的探讨阻塞性睡眠呼吸暂停综合征患者睡眠时肺动脉压的动态变化及不同睡眠时相对其的特异性影响。方法以１４例阻塞性睡眠呼吸暂停综合征患者为对象，采用肺动脉内留置ＳｗａｎＧａｎｚ导管并同步进行睡眠多导生理记录仪连续记录的方法。结果清醒时平均肺动脉压（ｍＰＡＰ）为２６９±１５３ｋＰａ（１ｋＰａ＝７．５ｍｍＨｇ），非快速动眼睡眠期（Ⅰ期和Ⅱ期）发生呼吸暂停时ｍＰＡＰ升至３４７±１６３ｋＰａ，快速动眼睡眠期呼吸暂停前后ｍＰＡＰ分别为３４７±２２１ｋＰａ和４７５±２４７ｋＰａ；快速动眼睡眠期发生呼吸暂停时ｍＰＡＰ升高１２８±０３６ｋＰａ，动脉血氧饱和度下降的幅度也明显大于非快速动眼睡眠期。结论阻塞性睡眠呼吸暂停综合征患者睡眠时的肺动脉压升高主要由呼吸暂停引起的肺泡缺氧所致     

A case of intestinal obstruction caused by strangulated femoral hernia accompanying soft tissue necrosis]

Intestinal obstruction involves a partial or complete blockage of the bowel which results in the failure of intestinal contents to pass through. The mechanical causes of obstruction may include the followings: hernias, postoperative adhesions or scar tissue, impacted feces, gallstones, tumors, granulomatous processes, intussusception, volvulus, foreign bodies, and etc. Hernias are the third leading cause of intestinal obstruction by 10% approximately. However, most hernias are the cases with abdominal wall, inguinal or internal hernia. Femoral, obturator, lumbar, or sciatic hernia as the cause of obsturction is rare. Furthermore, the cases accompanying soft tissue necrosis are seldomly reported. Herein, we report a case of intestinal obstruction caused by strangulated femoral hernia accompanying soft tissue necrosis in a 78-years-old female patient.     

Genetic and environmental control of host-gut microbiota interactions

Genetics provides a potentially powerful approach to dissect host-gut microbiota interactions. Toward this end, we profiled gut microbiota using 16s rRNA gene sequencing in a panel of 110 diverse inbred strains of mice. This panel has previously been studied for a wide range of metabolic traits and can be used for high-resolution association mapping. Using a SNP-based approach with a linear mixed model, we estimated the heritability of microbiota composition. We conclude that, in a controlled environment, the genetic background accounts for a substantial fraction of abundance of most common microbiota. The mice were previously studied for response to a high-fat, high-sucrose diet, and we hypothesized that the dietary response was determined in part by gut microbiota composition. We tested this using a cross-fostering strategy in which a strain showing a modest response, SWR, was seeded with microbiota from a strain showing a strong response, A×B19. Consistent with a role of microbiota in dietary response, the cross-fostered SWR pups exhibited a significantly increased response in weight gain. To examine specific microbiota contributing to the response, we identified various genera whose abundance correlated with dietary response. Among these, we chose Akkermansia muciniphila, a common anaerobe previously associated with metabolic effects. When administered to strain A×B19 by gavage, the dietary response was significantly blunted for obesity, plasma lipids, and insulin resistance. In an effort to further understand host-microbiota interactions, we mapped loci controlling microbiota composition and prioritized candidate genes. Our publicly available data provide a resource for future studies.Studies carried out over the last decade have revealed that gut microbiota contribute to a variety of common disorders, including obesity and diabetes (Musso et al. 2011), colitis (Devkota et al. 2012), atherosclerosis (Wang et al. 2011), rheumatoid arthritis (Vaahtovuo et al. 2008), and cancer (Yoshimoto et al. 2013). The evidence for metabolic interactions is particularly strong, as a large body of data now supports the conclusion that gut microbiota influence the energy harvest from dietary components, particularly complex carbohydrates, and that metabolites such as the short-chain fatty acids produced by gut bacteria can perturb metabolic traits, including adiposity and insulin resistance (Turnbaugh et al. 2006, 2009; Backhed et al. 2007; Wen et al. 2008; Ridaura et al. 2013). Gut microbiota communities are assembled each generation, influenced by maternal seeding, environmental factors, host genetics, and age, resulting in substantial variations in composition among individuals in human populations (Eckburg et al. 2005; Costello et al. 2009; Human Microbiome Project Consortium 2012; Goodrich et al. 2014). Most experimental studies of host-gut microbiota interactions have employed large perturbations, such as comparisons of germ-free versus conventional mice, and the significance of common variations in gut microbiota composition for disease susceptibility is still poorly understood. Furthermore, while studies with germ-free mice have clearly implicated microbiota in clinically relevant traits, it has proven difficult to identify the responsible taxa of bacteria.We now report a population-based analysis of host-gut microbiota interactions in the mouse. One of the issues we explore is the role of host genetics. Although some evidence is consistent with significant heritability of gut microbiota composition, the extent to which the host controls microbiota composition under controlled environmental conditions is unclear. We also examined the role of common variations in gut microbiota in metabolic traits such as obesity and insulin resistance and mapped loci contributing to the abundance of certain microbiota. We performed our study using a resource termed the Hybrid Mouse Diversity Panel (HMDP), consisting of about 100 inbred strains of mice that have been either sequenced or subjected to high-density genotyping (Bennett et al. 2010). The resource has several advantages for genetic analysis as compared to traditional genetic crosses. First, it allows high-resolution mapping by association rather than linkage analysis, and it has now been used for the identification of a number of novel genes underlying complex traits (Farber et al. 2011; Lavinsky et al. 2015; Parks et al. 2015; Rau et al. 2015). Second, since the strains are permanent, the data from separate studies can be integrated, allowing the development of large, publicly available databases of physiological and molecular traits relevant to a variety of clinical disorders (systems.genetics.ucla.edu and phenome.jax.org). Third, the panel is ideal for examining gene-by-environment interactions, since it is possible to examine individuals of a particular genotype under a variety of conditions (Orozco et al. 2012; Parks et al. 2013).     

Clear cell carcinoid of the appendix: Report of two cases with literature review

The clear cell/lipid‐rich change has been described in neuroendocine tumors in several organs, but rarely observed in the appendix. In this study, we describe the morphologic, immunohistochemical features of incidentally discovered appendiceal carcinoids entirely represented by clear cells in a 22‐year‐old man and a 52‐year‐old woman. Ultrastructual examination demonstrated abundant lipid droplets and dense core granules. The mechanism leading to lipid accumulation in the cytoplasm has not been discovered, but degenerative processes following recurrent inflammatory change might be considered. This uncommon variant of appendiceal classic carcinoid tumors may bear a superficial resemblance to goblet carcinoid and/or appendiceal metastases from clear cell carcinoma. Awareness of clear cell carcinoid of the appendix will prevent incorrect diagnosis and unnecessary aggressive management.     

Synthesis of a novel CO2-based alcohol amine compound and its usage in obtaining a water- and solvent-resistant coating

A five-membered cyclo-carbonate, prepared by cycloaddition reaction from CO₂ and 1,4-butanediol diglycidyl ether, was reacted with excessive diamine and formed a urethane group-containing new product. Structural characterization was performed for the new alcohol amine, which can be applied to the manufacture of polyurethane coatings as a chain extender. The new chain extender-based polyurethane coatings exhibited excellent water, salt, and solvent resistance and promising mechanical strength. Importantly, the unique performance of the prepared polyurethane coatings should be ascribed to the introduction of a hydroxyl group in the polyurethane molecule. The strengthened hydrogen bonding enlarged the cohesion of the polyurethane coatings and prohibited the solvents from permeating.

The novelty of the work: a water- and solvent-resistant coating was produced from a novel CO₂-based alcohol amine chain extender.     

Highly stretchable,mechanically stable,and weavable reduced graphene oxide yarn with high NO2 sensitivity for wearable gas sensors

Stretchable gas sensors are important components of wearable electronic devices used for human safety and healthcare applications. However, the current low stretchability and poor stability of the materials limit their use. Here, we report a highly stretchable, stable, and sensitive NO₂ gas sensor composed of reduced graphene oxide (RGO) sheets and highly elastic commercial yarns. To achieve high stretchability and good stability, the RGO sensors were fabricated using a pre-strain strategy (strain-release assembly). The fabricated stretchable RGO gas sensors showed high NO₂ sensitivity (55% at 5.0 ppm) under 200% strain and outstanding mechanical stability (even up to 5000 cycles at 400% applied strain), making them ideal for wearable electronic applications. In addition, our elastic graphene gas sensors can also be woven into fabrics and clothes for the creation of smart textiles. Finally, we successfully fabricated wearable gas-sensing wrist-bands from superelastic graphene yarns and stretchable knits to demonstrate a wearable electronic device.

Highly stretchable, mechanically stable and weavable RGO elastic electronic yarns were developed using dip-coating with pre-straining. We demonstrate wearable gas sensors that can be worn on the wrist.     

Blood-based immunoassay of tau proteins for early diagnosis of Alzheimer's disease using surface plasmon resonance fiber sensors

We present the immunoassay of tau proteins (total tau and phosphorylated tau) in human sera using surface plasmon resonance (SPR) fiber sensors. This assay aimed at harvesting the advantages of using both SPR fiber sensors and a blood-based assay to demonstrate label-free point-of-care-testing (POCT) patient-friendly assay in a compact format for the early diagnosis of Alzheimer''s disease (AD). For conducting the assay, we used human sera of 40 subjects divided into halves, which were grouped into AD patients and control groups according to a number of neuropsychological tests. We found that on an average, the concentrations of both total tau and phosphorylated tau proteins (all known to be higher in cerebrospinal fluid (CSF) and the brain) turned out to be higher in human sera of AD patients than in controls. The limits of detection of total tau and phosphorylated tau proteins were 2.4 pg mL⁻¹ and 1.6 pg mL⁻¹, respectively. In particular, it was found that the AD group exhibited average concentration of total tau proteins 6-fold higher than the control group, while concentration of phosphorylated tau proteins was 3-fold higher than that of the control. We can attribute this inhomogeneity between both types of tau proteins (in terms of increase of control-to-AD in average concentration) to un-phosphorylated tau proteins being more likely to be produced in blood than phosphorylated tau proteins, which possibly is one of the potential key elements playing an important role in AD progress.

Blood-based early diagnosis of Alzheimer''s disease using a plasmonic fiber sensor that detects immunoreaction of tau proteins.     

An environmentally sustainable plasticizer toughened polylactide

Cardanol (CD), derived from renewable natural cashew nutshell liquid, has been used as a new plasticizer for polylactide (PLA), to create blends which retain the environmentally friendly features of PLA. The differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and scanning electron microscopy (SEM) results all reveal that PLA and CD show good miscibility at low CD content. CD significantly decreased the glass transition temperature and enhanced the crystallization ability of PLA, demonstrating good plasticizing efficiency with PLA. At 10 wt% CD, ultimate elongation and impact toughness increased to 472% and 9.4 kJ m⁻², respectively, which represented improvements of 31-fold and 2.6-fold over the corresponding measurements for neat PLA. The plasticization effect of CD was also demonstrated by the decreased melt complex viscosity and shear storage modulus at lower CD content for the blends when compared with neat PLA. Thus, the investigated CD presents an interesting candidate for a PLA plasticizer, meeting “double green” criteria. No cytotoxicity was found for the blends and hence they may be suitable for biomedical applications.

Cardanol, derived from renewable resources, exhibits good plasticizing efficiency for PLA, meeting “double green” criteria.     

Speech perception in children with cochlear implants for continua varying in formant transition duration

Purpose: To examine the developmental course of labial and alveolar manner of articulation contrasts, and to determine how that course may be different for typically developing (TD) children with cochlear implants (CI).

Method: Eight young adults, eight TD 5–8 year-old children, and seven 5–8 year-old children with CIs participated. Labial /ba/–/wa/ and alveolar /da/–/ja/ continua stimuli were presented, with each continuum consisting of nine synthetic stimuli varying in F2 and F3 transition duration. Participants were asked to label the stimuli as either a stop or glide, and responses were analysed for phonetic boundaries and slopes.

Result: For the /ba/–/wa/ contrast, children with CIs required longer transition durations compared to TD children or adults to cross from one phoneme category to another. The children with CIs demonstrated less confidence in labelling the stimuli (i.e. less steep slopes) than the TD children or the adults. For the /da/–/ja/ contrast, the children with CIs showed less steep slope values than adults.

Conclusion: These results suggest that there are differences in the way TD children and children with CIs develop and maintain phonetic categories, perhaps differences in phonetic representation or in linking acoustic and phonetic representations.