cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.3123100
title: Data from: Response of migrating raptors to an increasing number of wind farms

description: Data associated to the manuscript with the same name. Dataset containing 1) total bird count per day during six consecutive autumn migratory seasons, 2) polar coordinates of soaring birds flight trajectories obtained through observations with marine radar, and 3) wind direction measured during the same six autumn seasons.<br><br><br>
DOI: 10.6084/m9.figshare.3123040
title: Summary of open source machine learning programs in QSAR

description: This table extracted from the below reference<br>Antonio Lavecchia. Machine-learning approaches in drug discovery: methods and applications. Volume 20, Issue 3, March 2015, Pages 318–331,Drug Discovery Today<br><br>
DOI: 10.6084/m9.figshare.3123040.v1
title: Summary of open source machine learning programs in QSAR

description: This table extracted from the below reference<br>Antonio Lavecchia. Machine-learning approaches in drug discovery: methods and applications. Volume 20, Issue 3, March 2015, Pages 318–331,Drug Discovery Today<br><br>
DOI: 10.6084/m9.figshare.3123100.v1
title: Response of migrating raptors to an increasing number of wind farms

description: Data associated to the manuscript with the same name. Dataset containing 1) total bird count per day during six consecutive autumn migratory seasons, 2) polar coordinates of soaring birds flight trajectories obtained through observations with marine radar, and 3) wind direction measured during the same six autumn seasons.<br><br><br>
DOI: 10.6084/m9.figshare.3123175.v2
title: Information, Time and the Human Mind

description: Quantum approaches to consciousness seem to explain several but not all observations in the field of mind-brain interaction. Information is introduced as a key to a wider world view since we have – according to Thomas Nagel –<i> to transcend the built-in limits of contemporary scientific orthodoxy </i>before we may <i>understand mind</i>. In the macroscopic world information is limited in contrast to the capability of our mind to work with unlimited information in mathematics. The world of mathematical concepts with unlimited information is independent of time and space and the mind is an intermediary between the macroscopic and the mathematical world. In the macroscopic world time is unidirectional while for the mind as well as in quantum physics time is bidirectional. In a given experimental system a photon carries 1 bit of information. Using a double slit gedankenexperiment it is shown that the transmission of the information from the photon to the detector takes the time span delta t = λ/c and Planck’s formula for the energy of the photon can be interpreted as Planck’s constant h multiplied by the elementary information flux (1bit) c/λ. The time span was determined by an observer in the macroscopic world. For the photon, however, time does not flow and space is shrunk to zero. For the discussion of time in quantum physical measurements these two viewpoints have to be distinguished. We may describe the photon as the elementary information unit in a world independent of time and space. The world of the photon is evidence for the existence of the world of mathematical concepts which is independent of time and space. When the information is transmitted from the world of the photon to the world of the detector it is absorbed and the loss of 1 bit information causes an increase of energy in the system. For complex information the hypothesis of an extended energy conservation law is formulated. An experimental test of the hypothetical equivalence of energy and information flux is necessary as a next step on the way which could lead to a better understanding of consciousness as well as to a quantitative theory of information.
DOI: 10.6084/m9.figshare.3123028
title: Gut Microbiome in Preterm Infants

description: Plos_one microbiome data <br>
DOI: 10.6084/m9.figshare.3123028.v1
title: Gut Microbiome in Preterm Infants

description: Plos_one microbiome data <br>
DOI: 10.6084/m9.figshare.3123175.v4
title: Information, Time and the Human Mind

description: Quantum approaches to consciousness seem to explain several but not all observations in the field of mind-brain interaction. Information is introduced as a key to a wider world view since we have – according to Thomas Nagel –<i> to transcend the built-in limits of contemporary scientific orthodoxy </i>before we may <i>understand mind</i>. In the macroscopic world information is limited in contrast to the capability of our mind to work with unlimited information in mathematics. The world of mathematical concepts with unlimited information is independent of time and space and the mind is an intermediary between the macroscopic and the mathematical world. In the macroscopic world time is unidirectional while for the mind as well as in quantum physics time is bidirectional. In a given experimental system a photon carries 1 bit of information. Using a double slit gedankenexperiment it is shown that the transmission of the information from the photon to the detector takes the time span delta t = λ/c and Planck’s formula for the energy of the photon can be interpreted as Planck’s constant h multiplied by the elementary information flux (1bit) c/λ. The time span was determined by an observer in the macroscopic world. For the photon, however, time does not flow and space is shrunk to zero. For the discussion of time in quantum physical measurements these two viewpoints have to be distinguished. We may describe the photon as the elementary information unit in a world independent of time and space. The world of the photon is evidence for the existence of the world of mathematical concepts which is independent of time and space. When the information is transmitted from the world of the photon to the world of the detector it is absorbed and the loss of 1 bit information causes an increase of energy in the system. For complex information the hypothesis of an extended energy conservation law is formulated. An experimental test of the hypothetical equivalence of energy and information flux is necessary as a next step on the way which could lead to a better understanding of consciousness as well as to a quantitative theory of information.
DOI: 10.4225/03/57428e1396239
title: The Crystal Structure of the Transthyretin-like Protein from Salmonella dublin, a Prokaryote 5-Hydroxyisourate Hydrolase (2GPZ)

description: The mechanism of binding of thyroid hormones by the transport protein transthyretin (TTR) in vertebrates is structurally well characterised. However, a homologous family of transthyretin-like proteins (TLPs) present in bacteria as well as eukaryotes do not bind thyroid hormones, instead they are postulated to perform a role in the purine degradation pathway and function as 5-hydroxyisourate hydrolases. Here we describe the 2.5 Angstroms X-ray crystal structure of the TLP from the Gram-negative bacterium Salmonella dublin, and compare and contrast its structure with vertebrate TTRs. The overall architecture of the homotetramer is conserved and, despite low sequence homology with vertebrate TTRs, structural differences within the monomer are restricted to flexible loop regions. However, sequence variation at the dimer-dimer interface has profound consequences for the ligand binding site and provides a structural rationalisation for the absence of thyroid hormone binding affinity in bacterial TLPs: the deep, negatively charged thyroxine-binding pocket that characterises vertebrate TTR contrasts with a shallow and elongated, positively charged cleft in S. dublin TLP. We have demonstrated that Sdu_TLP is a 5-hydroxyisourate hydrolase. Furthermore, using site-directed mutagenesis, we have identified three conserved residues located in this cleft that are critical to the enzyme activity. Together our data reveal that the active site of Sdu_TLP corresponds to the thyroxine binding site in TTRs.<br>
DOI: 10.6084/m9.figshare.3123175.v5
title: Information, Time and the Human Mind

description: Quantum approaches to consciousness seem to explain several but not all observations in the field of mind-brain interaction. Information is introduced as a key to a wider world view since we have – according to Thomas Nagel –<i> to transcend the built-in limits of contemporary scientific orthodoxy </i>before we may <i>understand mind</i>. In the macroscopic world information is limited in contrast to the capability of our mind to work with unlimited information in mathematics. The world of mathematical concepts with unlimited information is independent of time and space and the mind is an intermediary between the macroscopic and the mathematical world. In the macroscopic world time is unidirectional while for the mind as well as in quantum physics time is bidirectional. In a given experimental system a photon carries 1 bit of information. Using a double slit gedankenexperiment it is shown that the transmission of the information from the photon to the detector takes the time span delta t = λ/c and Planck’s formula for the energy of the photon can be interpreted as Planck’s constant h multiplied by the elementary information flux (1bit) c/λ. The time span was determined by an observer in the macroscopic world. For the photon, however, time does not flow and space is shrunk to zero. For the discussion of time in quantum physical measurements these two viewpoints have to be distinguished. We may describe the photon as the elementary information unit in a world independent of time and space. The world of the photon is evidence for the existence of the world of mathematical concepts which is independent of time and space. When the information is transmitted from the world of the photon to the world of the detector it is absorbed and the loss of 1 bit information causes an increase of energy in the system. For complex information the hypothesis of an extended energy conservation law is formulated. An experimental test of the hypothetical equivalence of energy and information flux is necessary as a next step on the way which could lead to a better understanding of consciousness as well as to a quantitative theory of information.
DOI: 10.4225/03/57428ddb6d6c8
title: X-ray crystal structure of the fibrinolysis inhibitor {alpha}2-antiplasmin (2R9Y)

description: The serpin alpha(2)-antiplasmin (SERPINF2) is the principal inhibitor of plasmin and inhibits fibrinolysis. Accordingly, alpha(2)-antiplasmin deficiency in humans results in uncontrolled fibrinolysis and a bleeding disorder. alpha(2)-antiplasmin is an unusual serpin, in that it contains extensive N- and C-terminal sequences flanking the serpin domain. The N-terminal sequence is crosslinked to fibrin by factor XIIIa, whereas the C-terminal region mediates the initial interaction with plasmin. To understand how this may happen, we have determined the 2.65A X-ray crystal structure of an N-terminal truncated murine alpha(2)-antiplasmin. The structure reveals that part of the C-terminal sequence is tightly associated with the body of the serpin. This would be anticipated to position the flexible plasmin-binding portion of the C-terminus in close proximity to the serpin Reactive Center Loop where it may act as a template to accelerate serpin/protease interactions.<br>
DOI: 10.4225/03/57428df17b655
title: The high resolution crystal structure of a native thermostable serpin reveals the complex mechanism underpinning the stressed to relaxed transition.

description: Serpins fold into a native metastable state and utilize a complex conformational change to inhibit target proteases. An undesirable result of this conformational flexibility is that most inhibitory serpins are heat sensitive, forming inactive polymers at elevated temperatures. However, the prokaryote serpin, thermopin, from Thermobifida fusca is able to function in a heated environment. We have determined the 1.8 A x-ray crystal structure of thermopin in the native, inhibitory conformation. A structural comparison with the previously determined 1.5 A structure of cleaved thermopin provides detailed insight into the complex mechanism of conformational change in serpins. Flexibility in the shutter region and electrostatic interactions at the top of the A beta-sheet (the breach) involving the C-terminal tail, a unique structural feature of thermopin, are postulated to be important for controlling inhibitory activity and triggering conformational change, respectively, in the native state. Here we have discussed the structural basis of how this serpin reconciles the thermodynamic instability necessary for function with the stability required to withstand elevated temperatures.<br>
DOI: 10.4225/03/57428dc49f1c4
title: Structure of the Plasmodium falciparum PfA-M17_Co4 (3KR5)

description: Current therapeutics and prophylactics for malaria are under severe challenge as a result of the rapid emergence of drug-resistant parasites. The human malaria parasite Plasmodium falciparum expresses two neutral aminopeptidases, PfA-M1 and PfA-M17, which function in regulating the intracellular pool of amino acids required for growth and development inside the red blood cell. These enzymes are essential for parasite viability and are validated therapeutic targets. We previously reported the X-ray crystal structure of the monomeric PfA-M1 and proposed a mechanism for substrate entry and free amino acid release from the active site. Here we present the X-ray crystal structure of the hexameric leucine aminopeptidase, PfA-M17, alone and in complex with two inhibitors with anti-malarial activity. The six active sites of the PfA-M17 hexamer are arranged in a disc-like fashion so that they are orientated inwards to form a central catalytic cavity; flexible loops that sit at each of the six entrances to the catalytic cavern function to regulate substrate access. In stark contrast to PfA-M1, PfA-M17 has a narrow and hydrophobic primary specificity pocket which accounts for its highly restricted substrate specificity. We also explicate the essential roles for the metal-binding centres in these enzymes (two in PfA-M17 and one in PfA-M1) in both substrate and drug binding. Our detailed understanding of the PfA-M1 and PfA-M17 active sites now permits a rational approach in the development of a novel class of two-target and/or combination anti-malarial therapy.<br>
DOI: 10.4225/03/57428d8357e3a
title: The structural basis for membrane binding and pore formation by lymphocyte perforin (3NSJ)

description: Natural killer cells and cytotoxic T lymphocytes accomplish the critically important function of killing virus-infected and neoplastic cells. They do this by releasing the pore-forming protein perforin and granzyme proteases from cytoplasmic granules into the cleft formed between the abutting killer and target cell membranes. Perforin, a 67-kilodalton multidomain protein, oligomerizes to form pores that deliver the pro-apoptopic granzymes into the cytosol of the target cell. The importance of perforin is highlighted by the fatal consequences of congenital perforin deficiency, with more than 50 different perforin mutations linked to familial haemophagocytic lymphohistiocytosis (type 2 FHL). Here we elucidate the mechanism of perforin pore formation by determining the X-ray crystal structure of monomeric murine perforin, together with a cryo-electron microscopy reconstruction of the entire perforin pore. Perforin is a thin ‘key-shaped’ molecule, comprising an amino-terminal membrane attack complex perforin-like (MACPF)/cholesterol dependent cytolysin (CDC) domain followed by an epidermal growth factor (EGF) domain that, together with the extreme carboxy-terminal sequence, forms a central shelf-like structure. A C-terminal C2 domain mediates initial, Ca2+-dependent membrane binding. Most unexpectedly, however, cryo-electron microscopy reveals that the orientation of the perforin MACPF domain in the pore is inside-out relative to the subunit arrangement in CDCs. These data reveal remarkable flexibility in the mechanism of action of the conserved MACPF/CDC fold and provide new insights into how related immune defence molecules such as complement proteins assemble into pores.<br>
DOI: 10.4225/03/57428d9acace2
title: X-ray crystal structure and specificity of the Plasmodium falciparum malaria aminopeptidase PfM18AAP

description: The malarial aminopeptidases have emerged as promising new drug targets for the development of novel anti-malarial drugs. The M18AAP of Plasmodium falciparum malaria is a metallo-aminopeptidase that we show demonstrates a highly restricted specificity for peptides with an N-terminal Glu or Asp residue. Thus the enzyme may function alongside other aminopeptidases in effecting the complete degradation or turnover of proteins, such as host hemoglobin, which provides a free amino acid pool for the growing parasite. Inhibition of PfM18AAP‚Äôs function using antisense RNA is detrimental to the intra-erythrocytic malaria parasite and, hence, it has been proposed as a potential novel drug target. We report the X-ray crystal structure of the PfM18AAP aminopeptidase and reveal its complex dodecameric assembly arranged via dimer and trimer units that interact to form a large tetrahedron shape that completely encloses the 12 active sites within a central cavity. The four entry points to the catalytic lumen are each guarded by 12 large flexible loops that could control substrate entry into the catalytic sites. PfM18AAP thus resembles a proteasomal-like machine with multiple active sites able to degrade peptide substrates that enter the central lumen. The Plasmodium enzyme shows significant structural differences around the active site when compared to recently determined structures of its mammalian and human homologs which provides a platform from which a rational approach to inhibitor design of new malaria-specific drugs can begin.<br>
DOI: 10.4225/03/57428daee3093
title: A bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases

description: Malaria causes worldwide morbidity and mortality, and while chemotherapy remains an excellent means of malaria control, drug-resistant parasites necessitate the discovery of new antimalarials. Peptidases are a promising class of drug targets and perform several important roles during the P. falciparum erythrocytic life cycle. Herein, we report a multidisciplinary effort combining activity-based protein profiling, biochemical, and peptidomic approaches to functionally analyze two genetically essential P. falciparum metallo-aminopeptidases (MAPs), PfA-M1 and Pf-LAP. Through the synthesis of a suite of activity-based probes (ABPs) based on the general MAP inhibitor scaffold, bestatin, we generated specific ABPs for these two enzymes. Specific inhibition of PfA-M1 caused swelling of the parasite digestive vacuole and prevented proteolysis of hemoglobin (Hb)-derived oligopeptides, likely starving the parasite resulting in death. In contrast, inhibition of Pf-LAP was lethal to parasites early in the lifecycle, prior to the onset of Hb degradation suggesting that Pf-LAP has an essential role outside of Hb digestion.<br>
DOI: 10.4225/03/57428d6aad18c
title: Bacterioferritin from Mycobacterium smegmatis contains zinc in its di-nuclear site. (3B3H)

description: The dataset contains 127 images collected at BM14 (ESRF Grenoble, France). Resolution of the final dataset is 2.71 A
DOI: 10.4225/03/57428d54e6bd4
title: The crystal structure of DehI reveals a new alpha-haloacid dehalogenase fold and active-site mechanism. (3BJX)

description: Haloacid dehalogenases catalyse the removal of halides from organic haloacids and are of interest for bioremediation and for their potential use in the synthesis of industrial chemicals. We present the crystal structure of the homodimer DehI from Pseudomonas putida strain PP3, the first structure of a group I alpha-haloacid dehalogenase that can process both l- and d-substrates. The structure shows that the DehI monomer consists of two domains of approximately 130 amino acids that have approximately 16% sequence identity yet adopt virtually identical and unique folds that form a pseudo-dimer. Analysis of the active site reveals the likely binding mode of both l- and d-substrates with respect to key catalytic residues. Asp189 is predicted to activate a water molecule for nucleophilic attack of the substrate chiral centre resulting in an inversion of configuration of either l- or d-substrates in contrast to d-only enzymes. These details will assist with future bioengineering of dehalogenases.<br>
DOI: 10.4225/03/57428d3d67ef1
title: A bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases (3T8V, 3T8W)

description: Malaria causes worldwide morbidity and mortality, and while chemotherapy remains an excellent means of malaria control, drug-resistant parasites necessitate the discovery of new antimalarials. Peptidases are a promising class of drug targets and perform several important roles during the P. falciparum erythrocytic life cycle. Herein, we report a multidisciplinary effort combining activity-based protein profiling, biochemical, and peptidomic approaches to functionally analyze two genetically essential P. falciparum metallo-aminopeptidases (MAPs), PfA-M1 and Pf-LAP. Through the synthesis of a suite of activity-based probes (ABPs) based on the general MAP inhibitor scaffold, bestatin, we generated specific ABPs for these two enzymes. Specific inhibition of PfA-M1 caused swelling of the parasite digestive vacuole and prevented proteolysis of hemoglobin (Hb)-derived oligopeptides, likely starving the parasite resulting in death. In contrast, inhibition of Pf-LAP was lethal to parasites early in the lifecycle, prior to the onset of Hb degradation suggesting that Pf-LAP has an essential role outside of Hb digestion.<br>
DOI: 10.4225/03/57428d0846d01
title: Structure of the Plasmodium falciparum PfA-M17 (3KQX)

description: Current therapeutics and prophylactics for malaria are under severe challenge as a result of the rapid emergence of drug-resistant parasites. The human malaria parasite Plasmodium falciparum expresses two neutral aminopeptidases, PfA-M1 and PfA-M17, which function in regulating the intracellular pool of amino acids required for growth and development inside the red blood cell. These enzymes are essential for parasite viability and are validated therapeutic targets. We previously reported the X-ray crystal structure of the monomeric PfA-M1 and proposed a mechanism for substrate entry and free amino acid release from the active site. Here we present the X-ray crystal structure of the hexameric leucine aminopeptidase, PfA-M17, alone and in complex with two inhibitors with anti-malarial activity. The six active sites of the PfA-M17 hexamer are arranged in a disc-like fashion so that they are orientated inwards to form a central catalytic cavity; flexible loops that sit at each of the six entrances to the catalytic cavern function to regulate substrate access. In stark contrast to PfA-M1, PfA-M17 has a narrow and hydrophobic primary specificity pocket which accounts for its highly restricted substrate specificity. We also explicate the essential roles for the metal-binding centres in these enzymes (two in PfA-M17 and one in PfA-M1) in both substrate and drug binding. Our detailed understanding of the PfA-M1 and PfA-M17 active sites now permits a rational approach in the development of a novel class of two-target and/or combination anti-malarial therapy.<br>