Local error estimates dramatically improve the utility of homology models for solving crystal structures by molecular replacement.

Predicted structures submitted for CASP10 have been evaluated as molecular replacement models against the corresponding sets of structure factor amplitudes. It has been found that the log-likelihood gain score computed for each prediction correlates well with common structure quality indicators but is more sensitive when the accuracy of the models is high. In addition, it was observed that using coordinate error estimates submitted by predictors to weight the model can improve its utility in molecular replacement dramatically, and several groups have been identified who reliably provide accurate error estimates that could be used to extend the application of molecular replacement for low-homology cases.Support received from the NIH (grant P01GM063210), the Wellcome Trust (Principal Research Fellowship to R.J.R., grant 082961/Z/07/Z; Strategic Award to the Cambridge Institute for Medical Research), as well as from the Swedish Research Council (621-2012-5270), Swedish e-Science Research Center, and Carl Tryggers Stiftelse to B.W. is gratefully acknowledged.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0969212614004146#

Pcons.net: protein structure prediction meta server

The Pcons.net Meta Server (http://pcons.net) provides improved automated tools for protein structure prediction and analysis using consensus. It essentially implements all the steps necessary to produce a high quality model of a protein. The whole process is fully automated and a potential user only submits the protein sequence. For PSI-BLAST detectable targets, an accurate model is generated within minutes of submission. For more difficult targets the sequence is automatically submitted to publicly available fold-recognition servers that use more advanced approaches to find distant structural homologs. The results from these servers are analyzed and assessed for structural correctness using Pcons and ProQ; and the user is presented with a ranked list of possible models. In addition, if the protein sequence contains more than one domain, these are automatically parsed out and resubmitted to the server as individual queries

Quantifying the geographical distribution effect on decreasing aggregated nitrogen oxides intensity in the Chinese electrical generation system

Over the past 20 years, the spatial distribution of electrical generation and its relationship to cross-regional power transmission has impacted China's power generation system and significantly affected the total amount of NO x and the aggregated nitrogen oxides intensity (ANI) of the system. An investigation of the driving mechanisms of ANI that considers the unevenness of regional electricity generation will be crucial to future improvements in the NO x efficiency of the electrical generation system in China. In this study, we built a decomposition model for ANI by incorporating the spatial distribution of electrical generation and found that the spatial distribution of electricity generation together with energy-related factors gradually caused decreases in ANI. The efficiency of electricity generation presented the dominant inhibitory effect on ANI, but its effect size has weakened since 2010. In contrast, the fossil fuel structure of thermal power shows an increasingly positive effect on changes in ANI. The primary energy composition only slightly affected changes in ANI. Moreover, the changed geographical distribution of electricity generation is non-negligible and has a positive effect on reduction of the ANI of the Chinese electrical generation system. The transferred amount of local NO x emissions by cross-provincial electricity transmission, however, could cause lead to additional environmental costs for generators. This issue should receive more attention in the future

An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12

Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly available at the WeFold website providing a wealth of data that remains to be tapped. Here, we analyze the results of the 2014 and 2016 pipelines showing improvements according to the CASP assessment as well as areas that require further adjustments and research

Charge Pair Interactions in Transmembrane Helices and Turn Propensity of the Connecting Sequence Promote Helical Hairpin Insertion

α-Helical hairpins, consisting of a pair of closely spaced transmembrane (TM) helices that are connected by a short interfacial turn, are the simplest structural motifs found in multi-spanning membrane proteins. In naturally occurring hairpins, the presence of polar residues is common and predicted to complicate membrane insertion. We postulate that the pre-packing process offsets any energetic cost of allocating polar and charged residues within the hydrophobic environment of biological membranes. Consistent with this idea, we provide here experimental evidence demonstrating that helical hairpin insertion into biological membranes can be driven by electrostatic interactions between closely separated, poorly hydrophobic sequences. Additionally, we observe that the integral hairpin can be stabilized by a short loop heavily populated by turn-promoting residues. We conclude that the combined effect of TM¿TM electrostatic interactions and tight turns plays an important role in generating the functional architecture of membrane proteins and propose that helical hairpin motifs can be acquired within the context of the Sec61 translocon at the early stages of membrane protein biosynthesis. Taken together, these data further underline the potential complexities involved in accurately predicting TM domains from primary structures

COVID-19. Pandemic surgery guidance

Abstract – Based on high quality surgery and scientific data, scientists and surgeons are committed to protecting patients as well as healthcare staff and hereby provide this Guidance to address the special issues circumstances related to the exponential spread of the Coronavirus disease 2019 (COVID-19) during this pandemic. As a basis, the authors used the British Intercollegiate General Surgery Guidance as well as recommendations from the USA, Asia, and Italy. The aim is to take responsibility and to provide guidance for surgery during the COVID-19 crisis in a simplified way addressing the practice of surgery, healthcare staff and patient safety and care. It is the responsibility of scientists and the surgical team to specify what is needed for the protection of patients and the affiliated healthcare team. During crises, such as the COVID-19 pandemic, the responsibility and duty to provide the necessary resources such as filters, Personal Protective Equipment (PPE) consisting of gloves, fluid resistant (Type IIR) surgical face masks (FRSM), filtering face pieces, class 3 (FFP3 masks), face shields and gowns (plastic ponchos), is typically left up to the hospital administration and government. Various scientists and clinicians from disparate specialties provided a Pandemic Surgery Guidance for surgical procedures by distinct surgical disciplines such as numerous cancer surgery disciplines, cardiothoracic surgery, ENT, eye, dermatology, emergency, endocrine surgery, general surgery, gynecology, neurosurgery, orthopedics, pediatric surgery, reconstructive and plastic surgery, surgical critical care, transplantation surgery, trauma surgery and urology, performing different surgeries, as well as laparoscopy, thoracoscopy and endoscopy. Any suggestions and corrections from colleagues will be very welcome as we are all involved and locked in a rapidly evolving process on increasing COVID-19 knowledg

Wnt Pathway in Bone Repair and Regeneration – What Do We Know So Far

Wnt signaling plays a central regulatory role across a remarkably diverse range of functions during embryonic development, including those involved in the formation of bone and cartilage. Wnt signaling continues to play a critical role in adult osteogenic differentiation of mesenchymal stem cells. Disruptions in this highly-conserved and complex system leads to various pathological conditions, including impaired bone healing, autoimmune diseases and malignant degeneration. For reconstructive surgeons, critically sized skeletal defects represent a major challenge. These are frequently associated with significant morbidity in both the recipient and donor sites. The Wnt pathway is an attractive therapeutic target with the potential to directly modulate stem cells responsible for skeletal tissue regeneration and promote bone growth, suggesting that Wnt factors could be used to promote bone healing after trauma. This review summarizes our current understanding of the essential role of the Wnt pathway in bone regeneration and repair

An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12

Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly available at the WeFold website providing a wealth of data that remains to be tapped. Here, we analyze the results of the 2014 and 2016 pipelines showing improvements according to the CASP assessment as well as areas that require further adjustments and research

Imagine a world without cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Since the War on Cancer was declared in 1971, the United States alone has expended some $300 billion on research, with a heavy focus on the role of genomics in anticancer therapy. Voluminous data have been collected and analyzed. However, in hindsight, any achievements made have not been realized in clinical practice in terms of overall survival or quality of life extended. This might be justified because cancer is not one disease but a conglomeration of multiple diseases, with widespread heterogeneity even within a single tumor type. Discussion Only a few types of cancer have been described that are associated with one major signaling pathway. This enabled the initial successful deployment of targeted therapy for such cancers. However, soon after this targeted approach was initiated, it was subverted as cancer cells learned and reacted to the initial treatments, oftentimes rendering the treatment less effective or even completely ineffective. During the past 30 plus years, the cancer classification used had, as its primary aim, the facilitation of communication and the exchange of information amongst those caring for cancer patients with the end goal of establishing a standardized approach for the diagnosis and treatment of cancers. This approach should be modified based on the recent research to affect a change from a service-based to an outcome-based approach. The vision of achieving long-term control and/or eradicating or curing cancer is far from being realized, but not impossible. In order to meet the challenges in getting there, any newly proposed anticancer strategy must integrate a personalized treatment outcome approach. This concept is predicated on tumor- and patient-associated variables, combined with an individualized response assessment strategy for therapy modification as suggested by the patients own results. As combined strategies may be outcome-orientated and integrate tumor-, patient- as well as cancer-preventive variables, this approach is likely to result in an optimized anticancer strategy. Summary Herein, we introduce such an anticancer strategy for all cancer patients, experts, and organizations: Imagine a World without Cancer