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A deep learning approach to prediction of blood group antigens from genomic data

Background: Deep learning methods are revolutionizing natural science. In this study, we aim to apply such techniques to develop blood type prediction models based on cheap to analyze and easily scalable screening array genotyping platforms. Methods: Combining existing blood types from blood banks and imputed screening array genotypes for ~111,000 Danish and 1168 Finnish blood donors, we used deep

“Every idea made life easier:” A critical discourse analysis of creative employee-driven innovation in the Italian healthcare system

Purpose: The purpose of this study is to scrutinize the connection between creativity and innovation in the context of public healthcare. This is achieved by applying the theoretical concept of employee-driven innovation (EDI) to explore employees’ perceptions of their creative engagement in innovation processes, as well as to capture the managerial implications of setting up such processes in the

Oxidative Stress and Its Biomarkers in Cardiovascular Diseases

Background: Cardiovascular diseases (CVDs) are the most common cause of death worldwide. CVDs share heterogeneous pathophysiologic mechanisms, one of which includes increased oxidative stress. Main Body: Surplus levels of reactive oxygen species induce damage to cellular macromolecules such as DNA, proteins, and lipids. Increased reactive oxygen species result in decreased nitric oxide availabilit

An immuno-inflammatory profiling of asymptomatic individuals in a malaria endemic area in Uganda

Malaria caused by Plasmodium falciparum leads to the destruction of red blood cells (RBCs). A better understanding of how naturally immune individuals control infections should be valuable for future vaccine studies. Antibodies against RBCs and RBC surface antigens were measured together with different inflammatory markers in healthy adults living in a malaria endemic area of Uganda and compared t

Synergistic effects of carbon coating and Bi-bridge in S-scheme C@CuO/Bi/Bi2MoO6 nanocomposites for enhanced photoreduction of Cr(VI)

The S-scheme mechanism in photocatalysis offers a promising approach to significantly enhance photoreductive activity. Here, using Bi dots as electronic media, and by changing the amount of added C@CuO on the surface of flower-shaped Bi2MoO6, a diverse range of CBM-x heterojunctions, were synthesized using a multi-step approach that incorporated solvothermal preparation and calcination methods. CB

Together but still alone - A qualitative study exploring how family members of persons with incurable oesophageal or gastric cancer manage everyday life

Background: Cancer affects not only the person with the disease but those around them. Being a family member is described as strenuous and, often, associated with stress, anxiety and feelings of loneliness. There is a heightened risk of distress for family of those with fast-progressing, severe oesophageal or gastric cancer. Early palliative care involving family is vital yet often overlooked. In

Dose conversion in retrospective dosimetry : Results and implications from an inter-laboratory comparison featuring a realistic exposure scenario

Dose conversion coefficients attempt to harmonize the material-, location-, and exposure-dependent results from retrospective dosemeters. The issues and uncertainties arising from dose conversion are explored within the framework of an interlaboratory comparison exercise in which mobile phones were positioned around anthropomorphic phantoms and exposed to non-uniform photon fields, with the glass

Exploring vacuum foam drying as an alternative to freeze-drying and spray drying for a human lipase

This article compares and explores vacuum foam-drying as an alternative drying technology to freeze-drying and spray drying for a recombinant human lipase as the model protein. Materials characteristics such as structure, surface composition and the solid-state properties of the dry materials were compared and investigated. Moreover, the technical functionality in terms of reconstitution character

Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888

Poly-ADP-ribose polymerases (PARPs) catalyze transfer of ADP-ribose from NAD(+) to specific residues in their substrate proteins or to growing ADP-ribose chains. PARP activity is involved in processes such as chromatin remodeling, transcription control, and DNA repair. Inhibitors of PARP activity may be useful in cancer therapy. PARP2 is the family member that is most similar to PARP1, and the two

Structure and function of a G-actin sequestering protein with a vital role in malaria oocyst development inside the mosquito vector

Cyclase-associated proteins (CAPs) are evolutionary conserved G-actin-binding proteins that regulate microfilament turnover. CAPs have a modular structure consisting of an N-terminal adenylate cyclase binding domain, a central proline-rich segment, and a C-terminal actin binding domain. Protozoan parasites of the phylum Apicomplexa, such as Cryptosporidium and the malaria parasite Plasmodium, expr

Crystal structures of the ATPase domains of four human Hsp70 isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78

The 70-kDa heat shock proteins (Hsp70) are chaperones with central roles in processes that involve polypeptide remodeling events. Hsp70 proteins consist of two major functional domains: an N-terminal nucleotide binding domain (NBD) with ATPase activity, and a C-terminal substrate binding domain (SBD). We present the first crystal structures of four human Hsp70 isoforms, those of the NBDs of HSPA1L

PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA

The PARP-3 protein is closely related to the PARP-1 and PARP-2 proteins, which are involved in DNA repair and genome maintenance. Here, we characterized the biochemical properties of human PARP-3. PARP-3 is able to ADP-ribosylate itself as well as histone H1, a previously unknown substrate for PARP-3. PARP-3 is not activated upon binding to DNA and is a mono-ADP-ribosylase, in contrast to PARP-1 a

Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7

Paraplegin is an m-AAA protease of the mitochondrial inner membrane that is linked to hereditary spastic paraplegias. The gene encodes an FtsH-homology protease domain in tandem with an AAA+ homology ATPase domain. The protein is believed to form a hexamer that uses ATPase-driven conformational changes in its AAA-domain to deliver substrate peptides to its protease domain. We present the crystal s

Vital role for the Plasmodium actin capping protein (CP) beta-subunit in motility of malaria sporozoites

Summary Successful malaria transmission from the mosquito vector to the mammalian host depends crucially on active sporozoite motility. Sporozoite locomotion and host cell invasion are driven by the parasite's own actin/myosin motor. A unique feature of this motor machinery is the presence of very short subpellicular actin filaments. Therefore, F-actin stabilizing proteins likely play a central ro

Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3

Poly(ADP-ribose) polymerases (PARPs) activate DNA repair mechanisms upon stress- and cytotoxin-induced DNA damage, and inhibition of PARP activity is a lead in cancer drug therapy. We present a structural and functional analysis of the PARP domain of human PARP-3 in complex with several inhibitors. Of these, KU0058948 is the strongest inhibitor of PARP-3 activity. The presented crystal structures

The DEXD/H-box RNA helicase DDX19 is regulated by an α-helical switch

DEXD/H-box RNA helicases couple ATP hydrolysis to RNA remodeling by an unknown mechanism. We used x-ray crystallography and biochemical analysis of the human DEXD/H-box protein DDX19 to investigate its regulatory mechanism. The crystal structures of DDX19, in its RNA-bound prehydrolysis and free posthydrolysis state, reveal an alpha-helix that inserts between the conserved domains of the free prot

Structural basis for parasite-specific functions of the divergent profilin of Plasmodium falciparum

Profilins are key regulators of actin dynamics. They sequester actin monomers, forming a pool for rapid polymer formation stimulated by proteins such as formins. Apicomplexan parasites utilize a highly specialized microfilament system for motility and host cell invasion. Their genomes encode only a small number of divergent actin regulators. We present the first crystal structure of an apicomplexa

Structural and functional characterization of human Iba proteins

Iba2 is a homolog of ionized calcium-binding adapter molecule 1 (Iba1), a 17-kDa protein that binds and cross-links filamentous actin (F-actin) and localizes to membrane ruffles and phagocytic cups. Here, we present the crystal structure of human Iba2 and its homodimerization properties, F-actin cross-linking activity, cellular localization and recruitment upon bacterial invasion in comparison wit

Structure-function analysis of the filamentous actin binding domain of the neuronal scaffolding protein spinophilin

Spinophilin, a neuronal scaffolding protein, is essential for synaptic transmission, and functions to target protein phosphatase-1 to distinct subcellular locations in dendritic spines. It is vital for the regulation of dendritic spine formation and motility, and functions by regulating glutamatergic receptors and binding to filamentous actin. To investigate its role in regulating actin cytoskelet