SEQATOMS: a web tool for identifying missing regions in PDB in sequence context.

doi:10.1093/nar/gkn23

Body image, cosmesis, quality of life, and functional outcome of hand-assisted laparoscopic versus open restorative proctocolectomy: long-term results of a randomized trial

BACKGROUND: This study aimed to compare quality of life (QOL), functional outcome, body image, and cosmesis after hand-assisted laparoscopic (LRP) versus open restorative proctocolectomy (ORP). The potential long-term advantages of LRP over ORP remain to be determined. The most likely advantage of LRP is the superior cosmetic result. It is, however, unclear whether the size and location of incisions affect body image and QOL. METHODS: In a previously conducted randomized trial comparing LRP with ORP, 60 patients were prospectively evaluated. The primary end points were body image and cosmesis. The secondary end points were morbidity, QOL, and functional outcome. A body image questionnaire was used to evaluate body image and cosmesis. The Short Form-36 Health Survey and the Gastrointestinal Quality of Life Inventory were used to assess QOL. Body image and QOL also were assessed preoperatively. RESULTS: A total of 53 patients completed the QOL and functional outcome questionnaires. There were no differences in functional outcome, morbidity, or QOL between LRP and ORP. At a median of 2.7 years after surgery, 46 patients returned the questionnaires regarding body image, cosmesis, and morbidity. The body image and cosmesis scores of female patients were significantly higher in the LRP group than in the ORP group (body image, 17.4 vs 14.9; cosmesis, 19.1 vs 13.0, respectively). The female patients in the ORP group had significantly lower body image scores than the male patients (14.9 vs 18.3). CONCLUSIONS: This study is the first to show that ORP has a negative impact on body image and cosmesis as compared with LRP. Functional outcome, QOL, and morbidity are similar for the two approaches. The advantages of a long-lasting improved body image and cosmesis for this relatively young patient population may compensate for the longer operating times and higher costs, particularly for wome

Secondary Structure, a Missing Component of Sequence- Based Minimotif Definitions

Minimotifs are short contiguous segments of proteins that have a known biological function. The hundreds of thousands of minimotifs discovered thus far are an important part of the theoretical understanding of the specificity of protein-protein interactions, posttranslational modifications, and signal transduction that occur in cells. However, a longstanding problem is that the different abstractions of the sequence definitions do not accurately capture the specificity, despite decades of effort by many labs. We present evidence that structure is an essential component of minimotif specificity, yet is not used in minimotif definitions. Our analysis of several known minimotifs as case studies, analysis of occurrences of minimotifs in structured and disordered regions of proteins, and review of the literature support a new model for minimotif definitions that includes sequence, structure, and function

Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD

An integrative environmental pollen diversity assessment and its importance for the Sustainable Development Goals

Pollen is at once intimately part of the reproductive cycle of seed plants and simultaneously highly relevant for the environment (pollinators, vector for nutrients, or organisms), people (food safety and health), and climate (cloud condensation nuclei and climate reconstruction). We provide an interdisciplinary perspective on the many and connected roles of pollen to foster a better integration of the currently disparate fields of pollen research, which would benefit from the sharing of general knowledge, technical advancements, or data processing solutions. We propose a more interdisciplinary and holistic research approach that encompasses total environmental pollen diversity (ePD) (wind and animal and occasionally water distributed pollen) at multiple levels of diversity (genotypic, phenotypic, physiological, chemical, and functional) across space and time. This interdisciplinary approach holds the potential to contribute to pressing human issues, including addressing United Nations Sustainable Development Goals, fostering social and political awareness of these tiny yet important and fascinating particles

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Comparing Models of Evolution for Ordered and Disordered Proteins

Most models of protein evolution are based upon proteins that form relatively rigid 3D structures. A significant fraction of proteins, the so-called disordered proteins, do not form rigid 3D structures and sample a broad conformational ensemble. Disordered proteins do not typically maintain long-range interactions, so the constraints on their evolution should be different than ordered proteins. To test this hypothesis, we developed and compared models of evolution for disordered and ordered proteins. Substitution matrices were constructed using the sequences of putative homologs for sets of experimentally characterized disordered and ordered proteins. Separate matrices, at three levels of sequence similarity (>85%, 85–60%, and 60–40%), were inferred for each type of protein structure. The substitution matrices for disordered and ordered proteins differed significantly at each level of sequence similarity. The disordered matrices reflected a greater likelihood of evolutionary changes, relative to the ordered matrices, and these changes involved nonconservative substitutions. Glutamic acid and asparagine were interesting exceptions to this result. Important differences between the substitutions that are accepted in disordered proteins relative to ordered proteins were also identified. In general, disordered proteins have fewer evolutionary constraints than ordered proteins. However, some residues like tryptophan and tyrosine are highly conserved in disordered proteins. This is due to their important role in forming protein–protein interfaces. Finally, the amino acid frequencies for disordered proteins, computed during the development of the matrices, were compared with amino acid frequencies for different categories of secondary structure in ordered proteins. The highest correlations were observed between the amino acid frequencies in disordered proteins and the solvent-exposed loops and turns of ordered proteins, supporting an emerging structural model for disordered proteins

Archaic chaos: intrinsically disordered proteins in Archaea

Background: Many proteins or their regions known as intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) lack unique 3D structure in their native states under physiological conditions yet fulfill key biological functions. Earlier bioinformatics studies showed that IDPs and IDRs are highly abundant in different proteomes and carry out mostly regulatory functions related to molecular recognition and signal transduction. Archaea belong to an intriguing domain of life whose members, being microbes, are characterized by a unique mosaic-like combination of bacterial and eukaryotic properties and include inhabitants of some of the most extreme environments on the planet. With the expansion of the archaea genome data (more than fifty archaea species from five different phyla are known now), and with recent improvements in the accuracy of intrinsic disorder prediction, it is time to re-examine the abundance of IDPs and IDRs in the archaea domain.Results: The abundance of IDPs and IDRs in 53 archaea species is analyzed. The amino acid composition profiles of these species are generally quite different from each other. The disordered content is highly species-dependent. Thermoproteales proteomes have 14% of disordered residues, while in Halobacteria, this value increases to 34%. In proteomes of these two phyla, proteins containing long disordered regions account for 12% and 46%, whereas 4% and 26% their proteins are wholly disordered. These three measures of disorder content are linearly correlated with each other at the genome level. There is a weak correlation between the environmental factors (such as salinity, pH and temperature of the habitats) and the abundance of intrinsic disorder in Archaea, with various environmental factors possessing different disorder-promoting strengths. Harsh environmental conditions, especially those combining several hostile factors, clearly favor increased disorder content. Intrinsic disorder is highly abundant in functional Pfam domains of the archaea origin. The analysis based on the disordered content and phylogenetic tree indicated diverse evolution of intrinsic disorder among various classes and species of Archaea.Conclusions: Archaea proteins are rich in intrinsic disorder. Some of these IDPs and IDRs likely evolve to help archaea to accommodate to their hostile habitats. Other archaean IDPs and IDRs possess crucial biological functions similar to those of the bacterial and eukaryotic IDPs/IDRs