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Immunogenetic variation in natural vertebrate populations is expected to respond to spatial and temporal fluctuations in pathogen assemblages. While spatial heterogeneity in pathogen-driven selection enhances local immunogenetic adaptations and population divergence, different immune genes may yield contrasting responses to the environment. Here, we investigated population differentiation at the key pathogen recognition genes of the innate and adaptive immune system in a colonial bird species, the black-headed gull Chroicocephalus ridibundus. We assessed genetic variation at three toll-like receptor (TLR) genes (innate immunity) and the major histocompatibility complex (MHC) class I and II genes (adaptive immunity) in gulls from seven colonies scattered across Poland. As expected, we found much greater polymorphism at the MHC than TLRs. Population differentiation at the MHC class II, but not MHC-I, was significantly stronger than at neutral microsatellite loci, suggesting local adaptation. This could reflect spatial variation in the composition of extracellular parasite communities (e.g., helminths), possibly driven by sharp differences in habitat structure between colonies. Despite contrasting patterns of population differentiation, both MHC classes showed similar regimes of diversifying selection. Some significant population differentiation was also observed at TLRs, suggesting that innate immune receptors may respond to fine-scale spatial variation in pathogen pressure, although this pattern could have been enhanced by drift. Our results suggested that local adaptation at the pathogen recognition immune genes can be maintained at relatively small or moderate spatial scales in species with high dispersal potential and they highlighted the complexity of immunogenetic responses of animals to heterogeneous environments., (© 2023. The Author(s), under exclusive licence to The Genetics Society.)

The aim of this study was to determine the effect of colostrum-supplemented transition milk on the growth rate of newborn calves. Thirty-six day-old female Holstein calves with a birth weight of 43.4 ± 5.5 kg were randomly assigned to a treatment group and a control group. On day 1, all calves received one portion (3 kg) of colostrum within 2 h after birth. Between the second feeding and the age of 5 days, control calves received only transition milk that had been collected from dams shortly before feeding, and the treatment group received 1.5 kg of colostrum collected from dams on day 1 and 1.5 kg of transition milk from subsequent milkings. Monthly body weight and average daily gain were used to measure growth performance. Blood samples were collected from the jugular vein at multiple time points to evaluate the biochemical and immune status of calves. Colostrum-supplemented transition milk increased the concentrations of serum immunoglobulins, triacylglycerols, cholesterol and total protein. The activity of lactate-dehydrogenase and ceruloplasmin decreased, whereas lysozyme activity increased with time in the control group. It can be concluded that additional five days of colostrum feeding positively influences non-specific humoral immunity indicators and serum biochemical parameters in dairy calves., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors.)

Acinetobacter baumannii is a worldwide occurring nosocomial pathogen, the natural habitats of which remain to be defined. Recently, white stork nestlings have been described as a recurring source of A. baumannii . Here, we challenged the hypothesis of a general preference of A. baumannii for avian hosts. Taking advantage of campaigns to ring free-living birds, we collected cloacal swab samples from 741 black-headed gulls ( Chroicocephalus ridibundus ) in Poland, tracheal and cloacal swabs from 285 songbirds in Poland as well as tracheal swabs from 25 songbirds in Slovenia and screened those for the growth of A. baumannii on CHROMagar TM Acinetobacter. Of the 1,051 samples collected only two yielded A. baumannii isolates. Each carried one variant of the bla OXA-51-like gene, i.e. OXA-71 and OXA-208, which have been described previously in clinical isolates of A. baumannii . In conclusion, our data do not support a general preference of A. baumannii for avian hosts., Acinetobacter baumannii is a worldwide occurring nosocomial pathogen, the natural habitats of which remain to be defined. Recently, white stork nestlings have been described as a recurring source of A. baumannii . Here, we challenged the hypothesis of a general preference of A. baumannii for avian hosts. Taking advantage of campaigns to ring free-living birds, we collected cloacal swab samples from 741 black-headed gulls ( Chroicocephalus ridibundus ) in Poland, tracheal and cloacal swabs from 285 songbirds in Poland as well as tracheal swabs from 25 songbirds in Slovenia and screened those for the growth of A. baumannii on CHROMagar TM Acinetobacter. Of the 1,051 samples collected only two yielded A. baumannii isolates. Each carried one variant of the bla OXA-51-like gene, i.e. OXA-71 and OXA-208, which have been described previously in clinical isolates of A. baumannii . In conclusion, our data do not support a general preference of A. baumannii for avian hosts.

Introduction: Trauma is the third cause of death among the general population in Poland, and the first in people aged 1-44 years. Trauma centers are hospitals dedicated to treating patients with multiple organ injuries, in a complex way that endeavours to ensure a lower mortality rate, shorter hospital stay and better outcomes if the patients are transferred to such a center. Worldwide, there are many models on how to treat a trauma patient, but them to be qualified for the procedure, the selection of potential patients is crucial., Objective: The aim of the study was to compare the Polish model for qualification to a trauma center and American Guidelines for Field Triage., Material and Methods: Retrospective analysis of medical documentation recorded between 1 January 2014 - 31 December 2014 was undertaken. The study concerned trauma patients admitted to the Emergency Department of the Regional Trauma Center at the Copernicus Memorial Hospital in Łódź, Poland. Inclusion criterion was initial diagnosis 'multiple-organ injury' among patients transported by the Emergency Medical Service (EMS)., Results: In the period indicated, 3,173 patients were admitted to the Emergency Department at the Copernicus Memorial Hospital. From among them, 159 patients were included in the study. Only 13.2% of the patients fulfilled the Polish Qualification Criteria to Trauma Center in comparison to 87.4% who fulfilled the American Guidelines for Field Triage., Conclusions: Polish qualification criteria do not consider the large group of patients with severe injuries (ISS>15), but indicate patients with minimal chance of survival. Polish criteria do not consider the mechanism of injury, which is a relevant predictive indicator of severe or extremely severe injuries (ISS>15). Further studies should be undertaken to improve the qualification and treatment of trauma patients in Poland.

In this Letter we describe the optimization of an aminopurine lead (1) with modest potency and poor overall kinase selectivity which led to the identification of a series of potent, selective JNK inhibitors. Improvement in kinase selectivity was enabled by introduction of an aliphatic side chain at the C-2 position. CC-359 (2) was selected as a potential clinical candidate for diseases manifested by ischemia reperfusion injury., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We determined a 1.95 A X-ray crystal structure of a C-terminally truncated Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT-18 protein) that functions in splicing group I introns. CYT-18's nucleotide binding fold and intermediate alpha-helical domains superimpose on those of bacterial TyrRSs, except for an N-terminal extension and two small insertions not found in nonsplicing bacterial enzymes. These additions surround the cyt-18-1 mutation site and are sites of suppressor mutations that restore splicing, but not synthetase activity. Highly constrained models based on directed hydroxyl radical cleavage assays show that the group I intron binds at a site formed in part by the three additions on the nucleotide binding fold surface opposite that which binds tRNATyr. Our results show how essential proteins can progressively evolve new functions.

DNA has proved to be a versatile material for the rational design and assembly of nanometer scale objects. Here we report the crystal structure of a continuous three-dimensional DNA lattice formed by the self-assembly of a DNA 13-mer. The structure consists of stacked layers of parallel helices with adjacent layers linked through parallel-stranded base pairing. The hexagonal lattice geometry contains solvent channels that appear large enough to allow 3'-linked guest molecules into the crystal. We have successfully used these parallel base pairs to design and produce crystals with greatly enlarged solvent channels. This lattice may have applications as a molecular scaffold for structure determination of guest molecules, as a molecular sieve, or in the assembly of molecular electronics. Predictable non-Watson-Crick base pairs, like those described here, may present a new tool in structural DNA nanotechnology.

The c-Kit proto-oncogene is a receptor protein-tyrosine kinase associated with several highly malignant human cancers. Upon binding its ligand, stem cell factor (SCF), c-Kit forms an active dimer that autophosphorylates itself and activates a signaling cascade that induces cell growth. Disease-causing human mutations that activate SCF-independent constitutive expression of c-Kit are found in acute myelogenous leukemia, human mast cell disease, and gastrointestinal stromal tumors. We report on the phosphorylation state and crystal structure of a c-Kit product complex. The c-Kit structure is in a fully active form, with ordered kinase activation and phosphate-binding loops. These results provide key insights into the molecular basis for c-Kit kinase transactivation to assist in the design of new competitive inhibitors targeting activated mutant forms of c-Kit that are resistant to current chemotherapy regimes.

Protein kinases are important drug targets in human cancers, inflammation, and metabolic diseases. This report presents the structures of kinase domains for three cancer-associated protein kinases: ephrin receptor A2 (EphA2), focal adhesion kinase (FAK), and Aurora-A. The expression profiles of EphA2, FAK, and Aurora-A in carcinomas suggest that inhibitors of these kinases may have inherent potential as therapeutic agents. The structures were determined from crystals grown in nanovolume droplets, which produced high-resolution diffraction data at 1.7, 1.9, and 2.3 A for FAK, Aurora-A, and EphA2, respectively. The FAK and Aurora-A structures are the first determined within two unique subfamilies of human kinases, and all three structures provide new insights into kinase regulation and the design of selective inhibitors.

Small protein B (SmpB) is an essential component of the highly conserved tmRNA-SmpB system that has the dual function of releasing stalled ribosomes from damaged messenger RNAs and targeting incompletely synthesized protein fragments for degradation. Nuclear magnetic resonance (NMR) analysis of SmpB from Aquifex aeolicus revealed an antiparallel beta-barrel structure, with three helices packed outside the core of the barrel. While the overall structure of SmpB appears to be unique, the structure does contain an embedded oligonucleotide binding fold; in this respect SmpB has similarity to several other RNA-binding proteins that are known to be associated with translation, including IF1, ribosomal protein S17 and the N-terminal domain of aspartyl tRNA synthetase. Conserved amino acids on the protein surface that are most likely to directly interact with the tmRNA were identified. The presence of widely separated clusters of conserved amino acids suggests that SmpB could function either by stabilizing two distal regions of the tmRNA, or by facilitating an interaction between the tmRNA and another component of the translational apparatus.