Whole-Brain Functional Connectivity Identification of Functional Dyspepsia

Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients’ dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course.     

Functional neuroimaging

Functional neuroimaging represents an area of brain imaging that has undergone tremendous advancements in the last decade. It is now possible to design experiments that elucidate the functional interplay between brain regions that give rise to specific human cognitive processes. Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) form the core technologies that have allowed such studies. This article reviews the basis of these techniques, their strengths and limitations, the underlying neurophysiology, and the future of functional neuroimaging.     

Functional amyloid

Evidence is growing at an increasing pace that amyloid fibers are not just the result of aberrant protein folding associated with neurodegenerative diseases, but are widespread in Nature for beneficial reasons. Amyloid is an attractive building material because its robust design and simple repetitive structure makes for very durable and metabolically cheap material. But this requires that the production of amyloid be put under firm control. This appears to involve the use of 4-5 chaperones which are expressed under the control of the same promoter as the amyloid proteins. Significant progress has been made in deciphering this process in E. coli’s csg operon, also found in Salmonella. Recently, we have discovered a new and unrelated operon (fap) responsible for amyloid production in Pseudomonas, which also confers biofilm forming properties to E. coli. Intriguingly, this operon shares a number of features with csg, namely two homologous proteins (one of which, FapC, has been shown to be directly involved in amyloid build-up) and a small number of auxiliary proteins. However, FapC seems to be less economically structured than its E. coli counterpart, with a smaller number of repeats and very large and variable linker regions. Furthermore, the putative chaperones are not homologous to their csg counterparts and have intriguing homologies to proteins with other functions. These findings suggest that controlled amyloid production has arisen on many independent occasions due to the usefulness of the product and offers the potential for intriguing insights into how Nature disarms and reconstructs a potentially very dangerous weapon.     

Functional evo-devo

Functional factors such as optimal design and adaptive value have been the central concern of evolutionary biology since the advent of the New Synthesis. By contrast, evolutionary developmental biology (evo-devo) has concentrated primarily on structural factors such as the ways in which body parts can be built. These different emphases have stood in the way of an integrated understanding of the role of development in evolution. Here, we try to bridge this gap by outlining the relevance of functional factors in evo-devo. We use modularity and the view of development as a flexible evolutionary system to outline a unified perspective that includes both structural and functional aspects.     

重组人白介素6受体功能区片段的功能鉴定

用生物素标记重组人白介素6受体功能区片段rIL6R-28及其二联体蛋白rIL6R-53．竞争ELISA表明重组蛋白可以与配基IL-6特异结合．流式细胞术检测结果表明IL-6与生物素标记的重组蛋白所形成的复合物能够与7TD1细胞表面的gp130结合．而7TD1细胞生长分析则表明,重组蛋白可以增强IL-6对7TD1．细胞的生长刺激作用．     

Functional studies of eppin

Our laboratory has characterized EPPIN [epididymal protease inhibitor; SPINLW1] as a novel gene on human chromosome 20q12-13.2, which encodes a cysteine-rich protein of 133 amino acids with a calculated molecular mass of 15.283?kDa, containing both Kunitz-type and WAP (whey acidic protein)-type four-disulfide core consensus sequences. Eppin is secreted by Sertoli cells in the testis and epididymal epithelial cells; it is predominantly a dimer, although multimers often exist, and in its native form eppin is found on the human sperm surface complexed with LTF (lactotransferrin) and clusterin. During ejaculation SEMG (semenogelin) from the seminal vesicles binds to the eppin protein complex, initiating a series of events that define eppin's function. Eppin's functions include (i) modulating PSA (prostate-specific antigen) enzyme activity, (ii) providing antimicrobial protection and (iii) binding SEMG thereby inhibiting sperm motility. As PSA hydrolyses SEMG in the ejaculate coagulum, spermatozoa gain progressive motility. We have demonstrated that eppin is essential for fertility because immunization of male monkeys with recombinant eppin results in complete, but reversible, contraception. To exploit our understanding of eppin's function, we are developing compounds that inhibit eppin-SEMG interaction and mimic anti-eppin, inhibiting sperm motility. These compounds should have potential as a male contraceptive.     

Functional symmetry of endomembranes

In higher eukaryotic cells pleiomorphic compartments composed of vacuoles, tubules and vesicles move from the endoplasmic reticulum (ER) and the plasma membrane to the cell center, operating in early biosynthetic trafficking and endocytosis, respectively. Besides transporting cargo to the Golgi apparatus and lysosomes, a major task of these compartments is to promote extensive membrane recycling. The endocytic membrane system is traditionally divided into early (sorting) endosomes, late endosomes and the endocytic recycling compartment (ERC). Recent studies on the intermediate compartment (IC) between the ER and the Golgi apparatus suggest that it also consists of peripheral ("early") and centralized ("late") structures, as well as a third component, designated here as the biosynthetic recycling compartment (BRC). We propose that the ERC and the BRC exist as long-lived "mirror compartments" at the cell center that also share the ability to expand and become mobilized during cell activation. These considerations emphasize the functional symmetry of endomembrane compartments, which provides a basis for the membrane rearrangements taking place during cell division, polarization, and differentiation.     

Functional diversity of dystroglycan

During the last 15 years, following its identification and first detailed molecular characterization, the dystroglycan (DG) complex has taken centre stage in biology and biomedicine. Functions in different cells and tissues have been identified for this complex, ranging from its typical role in skeletal muscle as a sarcolemmal stabilizer, highlighted by the recently identified “secondary dystroglycanopathies”, to a variety of very diverse functions including embryogenesis, cancer progression, virus particle entry and cell signalling. Such functional promiscuity can be in part explained when considering the multiple domain organization of the two DG subunits, the extracellular α-DG and the transmembrane β-DG, that has been largely scrutinized, but only in part unraveled, exploiting a variety of recombinant and transgenic approaches. Herein, while rapidly recapitulating some of the functions that nowadays can be assigned safely to each DG domain, we also try to envisage a sort of worry list featuring and dwelling on some of the most compelling ”mysteries” that should be solved to finally understand DG's functional diversity.     

Functional Connectivity Alterations in Epilepsy from Resting-State Functional MRI

The study of functional brain connectivity alterations induced by neurological disorders and their analysis from resting state functional Magnetic Resonance Imaging (rfMRI) is generally considered to be a challenging task. The main challenge lies in determining and interpreting the large-scale connectivity of brain regions when studying neurological disorders such as epilepsy. We tackle this challenging task by studying the cortical region connectivity using a novel approach for clustering the rfMRI time series signals and by identifying discriminant functional connections using a novel difference statistic measure. The proposed approach is then used in conjunction with the difference statistic to conduct automatic classification experiments for epileptic and healthy subjects using the rfMRI data. Our results show that the proposed difference statistic measure has the potential to extract promising discriminant neuroimaging markers. The extracted neuroimaging markers yield 93.08% classification accuracy on unseen data as compared to 80.20% accuracy on the same dataset by a recent state-of-the-art algorithm. The results demonstrate that for epilepsy the proposed approach confirms known functional connectivity alterations between cortical regions, reveals some new connectivity alterations, suggests potential neuroimaging markers, and predicts epilepsy with high accuracy from rfMRI scans.     

基因的功能冗余

1　冗余的定义对于特定的一个系统以及该系统的各种组成部件 ,其寿命总是有限的 ,不可避免地会发生故障。为了确保系统的正常运转 ,必须为系统配制一定数量的备用零件 ,即构成所谓的冗余[3 ] 。没有冗余的系统是脆弱的 ,经不起外界随机事件的干扰 ,必须具有足够的冗余 ,它才能维持其结构和功能的正常进行。冗余 (ｒｅｄｕｎｄａｎｃｅ)这一概念来源于自动控制系统可靠性理论[1] 。系统是由不同的元件 (成分 )组成的 ,元件的组合方式与系统的可靠性关系十分密切。按元件组合方式可把系统分为串联系统和并联系统。在串联系统中 ,当系统的元件…