Fibrillin protein function: the tip of the iceberg?

Fibrillins are nuclear-encoded, plastid proteins associated with chromoplast fibrils and chloroplast plastoglobules, thylakoids, photosynthetic antenna complexes, and stroma. There are 12 sub-families of fibrillins. However, only three of these sub-families have been characterized genetically or functionally. We review evidence indicating that fibrillins are involved in plastoglobule structural development, chromoplast pigment accumulation, hormonal responses, protection of the photosynthetic apparatus from photodamage, and plant resistance to a range of biotic and abiotic stresses. The area of fibrillin research has substantial growth potential and will contribute to better understanding of mechanisms of plant stress tolerance and plastid structure and function.     

The protein–protein interaction network of the human Sirtuin family

Protein–protein interaction networks are useful for studying human diseases and to look for possible health care through a holistic approach. Networks are playing an increasing and important role in the understanding of physiological processes such as homeostasis, signaling, spatial and temporal organizations, and pathological conditions. In this article we show the complex system of interactions determined by human Sirtuins (Sirt) largely involved in many metabolic processes as well as in different diseases. The Sirtuin family consists of seven homologous Sirt-s having structurally similar cores but different terminal segments, being rather variable in length and/or intrinsically disordered. Many studies have determined their cellular location as well as biological functions although molecular mechanisms through which they act are actually little known therefore, the aim of this work was to define, explore and understand the Sirtuin-related human interactome. As a first step, we have integrated the experimentally determined protein–protein interactions of the Sirtuin-family as well as their first and second neighbors to a Sirtuin-related sub-interactome. Our data showed that the second-neighbor network of Sirtuins encompasses 25% of the entire human interactome, and exhibits a scale-free degree distribution and interconnectedness among top degree nodes. Moreover, the Sirtuin sub interactome showed a modular structure around the core comprising mixed functions. Finally, we extracted from the Sirtuin sub-interactome subnets related to cancer, aging and post-translational modifications for information on key nodes and topological space of the subnets in the Sirt family network.     

RNA-binding proteins in plants: the tip of an iceberg?

RNA-binding proteins, which are involved in the synthesis, processing, transport, translation, and degradation of RNA, are emerging as important, often multifunctional, cellular regulatory proteins. Although relatively few RNA-binding proteins have been studied in plants, they are being identified with increasing frequency, both genetically and biochemically. RNA-binding proteins that regulate chloroplast mRNA stability and translation in response to light and that have been elegantly analyzed in Clamydomonas reinhardtii have counterparts with similar functions in higher plants. Several recent reports describe mutations in genes encoding RNA-binding proteins that affect plant development and hormone signaling.     

Antinuclear antibodies in healthy people: the tip of autoimmunity's iceberg?

Antinuclear antibodies (ANAs) are venerable biomarkers for assessing the diagnosis and prognosis of patients with autoimmunity. While closely associated with diseases such as systemic lupus erythematosus, ANA expression occurs commonly in healthy people. The basis for this expression is unknown, although it may reflect features of the assays for antibody detection or intrinsic immunological disturbances in otherwise normal individuals. Like autoimmunity itself, ANA expression is more common among women than men, pointing to an important determinant of these responses. Future research will clarify the mechanisms of ANA expression and the utility of current assays as antecedent and screening biomarkers.     

ModuleSearch: finding functional modules in a protein–protein interaction network

Many biological processes are performed by a group of proteins rather than by individual proteins. Proteins involved in the same biological process often form a densely connected sub-graph in a protein–protein interaction network. Therefore, finding a dense sub-graph provides useful information to predict the function or protein complex of uncharacterised proteins in the sub-graph. We developed a heuristic algorithm that finds functional modules in a protein–protein interaction network and visualises the modules. The algorithm has been implemented in a platform-independent, standalone program called ModuleSearch. In an interaction network of yeast proteins, ModuleSearch found 366 overlapping modules. Of the modules, 71% have a function shared by more than half the proteins in the module and 58% have a function shared by all proteins in the module. Comparison of ModuleSearch with other programs shows that ModuleSearch finds more sub-graphs than most other programs, yet a higher proportion of the sub-graphs correspond to known functional modules. ModuleSearch and sample data are freely available to academics at http://bclab.inha.ac.kr/ModuleSearch.     

Human infections with Dicrocoelium dendriticum in Kyrgyzstan: the tip of the iceberg?

Dicrocoelium dendriticum is the causative agent of a rare food-borne zoonosis of the human biliary tract, dicrocoeliasis, for which few human prevalence data are available. Infection occurs through the ingestion of ants containing metacercariae, whereas pseudo-infections (presence of D. dendriticum eggs in stool in the absence of adult worms) are due to the consumption of infected animal liver. Here, results from a cross-sectional survey carried out among 138 children aged 2-15 yr in a peri-urban area of Kyrgyzstan are reported. Each child provided 1 stool sample that was subjected to the FLOTAC technique. Eggs of D. dendriticum were diagnosed in 11 children (prevalence 8.0%; 95% confidence interval 4.5-13.7%). Although no distinction could be made between true and pseudo-infections, the prevailing animal husbandry system and the diet and hygienic conditions of the study area suggest that the social-ecological system in Kyrgyzstan is conducive for human transmission of D. dendriticum. There is a need to investigate the epidemiology of dicrocoeliasis in Kyrgyzstan, placing emphasis on the distinction between true and pseudo-infections.     

The ‘shifting baseline’ phenomenon: a global perspective

In this paper we demonstrate that low level ‘artisanal’ fishing can dramatically affect populations of slow-growing, late-maturing animals and that even on remote oceanic islands, stocks have been depleted and ecosystems degraded for millennia. Industrialised fisheries have developed during different decades in different regions of the world, and this has almost always been followed by a period of massive stock decline. However, ecosystems were not pristine before the onset of industrial fishing and it is difficult to assess the ‘virgin’ state of a population given that it may have been subject to moderate or even high levels of fishing mortality for many centuries. A wide range of information is available to help define or deduce historic marine population status. These include ‘traditional’ written sources but also less conventional sources such as archaeological remains, genetic analyses or simple anecdotal evidence. Detailed information, collected specifically for the purpose of determining fish stock biomass tends to exist only for recent decades, and most fishery assessments around the world (and thus time-series of biomass estimates), are less than 30 years long. Here we advocate using a wider range of multidisciplinary data sources, although we also recognise that it can be difficult to separate natural variability associated with changing climatic conditions from human-induced changes through fishing. We consider whether or not recovery of degraded ecosystems is ever possible and discuss a series of one-way ratchet like processes that can make it extremely difficult to return to a former ecosystem state.     

Lateral gene transfer in eukaryotes: tip of the iceberg or of the ice cube?

Lateral gene transfer (LGT) is the transmission of genes, sometimes across species barriers, outwith the classic vertical inheritance from parent to offspring. LGT is recognized as an important phenomenon that has shaped the genomes and biology of prokaryotes. Whether LGT in eukaryotes is important and widespread remains controversial. A study in BMC Biology concludes that LGT in eukaryotes is neither continuous nor prevalent and suggests a rule of thumb for judging when apparent LGT may reflect contamination.See research article: http://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0315-9.     

Function of the IsiA pigment–protein complex in vivo

Photosynthesis Research - The acclimation of cyanobacterial photosynthetic apparatus to iron deficiency is crucial for their performance under limiting conditions. In many cyanobacterial species,...     

The RecQ helicase–topoisomerase III–Rmi1 complex: a DNA structure-specific ‘dissolvasome’?

RecQ helicases, together with topoisomerase III and Rmi1 family proteins, form an evolutionarily conserved complex that is essential for the maintenance of genome integrity. This complex, which we term RTR, is capable of, or has been implicated in, the processing of a diverse array of DNA structures, and we propose here that it functions in a coordinated fashion as a DNA structure-specific 'dissolvasome'. Little is known about how the RTR complex might be regulated or targeted to various DNA structures in vivo. Recent findings indicate that the components of the RTR complex might activate the cell cycle checkpoint machinery as well as be a target of checkpoint kinases, suggesting that these events are crucial to ensure faithful DNA replication and chromosome segregation.     

Discovery of a small-molecule inhibitor and cellular probe of Keap1–Nrf2 protein–protein interaction

A high-throughput screen (HTS) of the MLPCN library using a homogenous fluorescence polarization assay identified a small molecule as a first-in-class direct inhibitor of Keap1–Nrf2 protein–protein interaction. The HTS hit has three chiral centers; a combination of flash and chiral chromatographic separation demonstrated that Keap1-binding activity resides predominantly in one stereoisomer (SRS)-5 designated as ML334 (LH601A), which is at least 100× more potent than the other stereoisomers. The stereochemistry of the four cis isomers was assigned using X-ray crystallography and confirmed using stereospecific synthesis. (SRS)-5 is functionally active in both an ARE gene reporter assay and an Nrf2 nuclear translocation assay. The stereospecific nature of binding between (SRS)-5 and Keap1 as well as the preliminary but tractable structure–activity relationships support its use as a lead for our ongoing optimization     

Role of MERIT40 in stabilization of BRCA1 complex: A protein–protein interaction study

MERIT40 is a novel associate of the BRCA1-complex, thus play an essential role in DNA damage repair mechanism. It is the least implicit protein and its structural and functional aspects of regulating the stability of BRCA1–MERIT40 complex remain equivocal. Analysis of protein–protein interactions between BRCA1 and its cellular binding partners like ABRAXAS, RAP80 and MERIT40 would help to understand the role of protein complex integrity in DNA repair mechanism. The recombinant proteins were purified and their structural aspects were elucidated by spectroscopic methods. Interaction analysis was carried out to determine binding partners of MERIT40. MERIT40 showed interaction with bridging molecule, called ABRAXAS, thus generate a scaffold among various members which further stabilizes the entire complex. It acts as an adapter molecule by interacting with BRCA1-BRCT in non-phosphorylation dependent manner. The feature enlighten on structural and interaction profile of BRCA1-complex member to elucidate their role in complex stability and DNA repair process.     

The protein–polysaccharide complex of bovine nasal cartilage. Studies on the protein core

1. Chondromucoprotein from bovine nasal cartilage was purified by cetylpyridinium chloride or by bismuth nitrate in acetone. 2. Amino acid compositions of crude and purified preparations were compared and few differences were found, in spite of the decrease in protein content on purification. 3. Amino acid analysis of bismuth-purified material revealed the existence of four groups of amino acids. Within each group, the amino acids were present in approximately equimolar concentrations. 4. Amino end-group assay on the same material showed six alpha-DNP derivatives. 5. A molecular weight of 6.3x10(5) for the protein-polysaccharide complex was calculated from the latter analysis.     

The transformation of the cytoplasmic oestradiol–receptor complex into the nuclear complex in a uterine cell-free system

Experiments performed with a cell-free system in tris-EDTA buffer, pH 7.4, indicate that the high-speed supernatant fraction of the rat uterus contains all the factors necessary to transform the 8S cytoplasmic oestradiol-receptor complex to the nuclear complex. The transformation is temperature-dependent. This nuclear complex was extracted in the form of a 5S particle with 0.4m-KCl from sediments of either uterine or heart nuclei that had been incubated together with the cytoplasmic soluble fraction of the uterus at 2 degrees C for 30min. This complex can also be obtained similarly from the soluble fraction of the uterus, incubated in the absence of nuclei. Previous warming of the soluble fraction to 37 degrees C for 7min was necessary for the successful extraction of the nuclear particle under these conditions of incubation. After an incubation of the transformed complex with the nuclear sediment at 37 degrees C for 7min, the 5S complex was extractable from the uterine nuclear sediment but not from the heart nuclear sediment, which may indicate the tissue specificity of the nuclear acceptor sites for the transformed complex. The extracted uterine nuclear complex sediments in the 5S region, but whether it is the native complex or a subunit or other part of the native complex resulting from the extraction with salt is unknown.     

The ‘Psychic Surgeon’ and the schizophrenic patient: Crisis in a ‘Medicodrama’

This paper is concerned with a Filipino psychic surgeon confronted by a particularly challenging case of a kind perhaps unprecedented in his practice. The paper describes and analyzes how the practitioner modified his usual clinical performance and adapted his actions to demands of an extremely difficult situation. The case is viewed in wider perspective relative to the significance of performative acts of healing in a pluralistic medical setting.     

An analysis of a ‘community-driven’ reconstruction of the human metabolic network

Following a strategy similar to that used in baker’s yeast (Herrgård et al. Nat Biotechnol 26:1155–1160, 2008). A consensus yeast metabolic network obtained from a community approach to systems biology (Herrgård et al. 2008; Dobson et al. BMC Syst Biol 4:145, 2010). Further developments towards a genome-scale metabolic model of yeast (Dobson et al. 2010; Heavner et al. BMC Syst Biol 6:55, 2012). Yeast 5—an expanded reconstruction of the Saccharomyces cerevisiae metabolic network (Heavner et al. 2012) and in Salmonella typhimurium (Thiele et al. BMC Syst Biol 5:8, 2011). A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella typhimurium LT2 (Thiele et al. 2011), a recent paper (Thiele et al. Nat Biotechnol 31:419–425, 2013). A community-driven global reconstruction of human metabolism (Thiele et al. 2013) described a much improved ‘community consensus’ reconstruction of the human metabolic network, called Recon 2, and the authors (that include the present ones) have made it freely available via a database at http://humanmetabolism.org/ and in SBML format at Biomodels (http://identifiers.org/biomodels.db/MODEL1109130000). This short analysis summarises the main findings, and suggests some approaches that will be able to exploit the availability of this model to advantage.     

The role of protein–solvent hydrogen bond dynamics in the structural relaxation of a protein in glycerol versus water

We used MD simulations to investigate the dependence of the dynamics of a soluble protein, RNase A, on temperature and solvent environment. Consistent with neutron scattering data, the simulations predict that the protein undergoes a dynamical transition in both glycerol and aqueous solutions that is absent in the dry protein. The temperature of the transition is higher, while the rate of increase with temperature of the amplitudes of motion on the 100 ps timescale is lower, in glycerol versus water. Analysis of the dynamics of hydrogen bonds revealed that the protein dynamical transition is connected to the relaxation of the protein-solvent hydrogen bond network, which, in turn, is associated with solvent translational diffusion. Thus, it appears that the role of solvent dynamics in affecting the protein dynamical transition is qualitatively similar in water and glycerol.