Polarization-Sensitive Photoluminescence from Aligned Carbon Chains Terminated by Gold Clusters.

We synthesize a thin film composed of long carbyne chains terminated by gold clusters and study its optical properties. The presence of gold particles stabilizes longer chains and leads to their alignment. We show that the gold clusters also act as a source of electron doping, thus, changing the intensity of photoluminescence from quadratic dependence on the pumping intensity without gold to linear with gold. We also observe that the excitation of the film at the gold plasmon frequency causes the blue shift of photoluminescence and estimate, on the basis of this effect, the minimum length of the carbyne chains. The high degree of alignment of the gold-terminated carbyne chains results in strongly anisotropic light absorption characterized by a distinctive cosine dependence on the angle between the carbyne molecule and polarization plane of the excitation. This paves the way for a new class of ultimately thin polarization sensitive emitters to be used in future integrated quantum photonics devices.

Upregulation of virulence genes promotes Vibrio cholerae biofilm hyperinfectivity.

Vibrio cholerae remains a major global health threat, disproportionately impacting parts of the world without adequate infrastructure and sanitation resources. In aquatic environments, V. cholerae exists both as planktonic cells and as biofilms, which are held together by an extracellular matrix. V. cholerae biofilms have been shown to be hyperinfective, but the mechanism of hyperinfectivity is unclear. Here we show that biofilm-grown cells, irrespective of the surfaces on which they are formed, are able to markedly outcompete planktonic-grown cells in the infant mouse. Using an imaging technique designed to render intestinal tissue optically transparent and preserve the spatial integrity of infected intestines, we reveal and compare three-dimensional V. cholerae colonization patterns of planktonic-grown and biofilm-grown cells. Quantitative image analyses show that V. cholerae colonizes mainly the medial portion of the small intestine and that both the abundance and localization patterns of biofilm-grown cells differ from that of planktonic-grown cells. In vitro biofilm-grown cells activate expression of the virulence cascade, including the toxin coregulated pilus (TCP), and are able to acquire the cholera toxin-carrying CTXФ phage. Overall, virulence factor gene expression is also higher in vivo when infected with biofilm-grown cells, and modulation of their regulation is sufficient to cause the biofilm hyperinfectivity phenotype. Together, these results indicate that the altered biogeography of biofilm-grown cells and their enhanced production of virulence factors in the intestine underpin the biofilm hyperinfectivity phenotype.

[Critical aspects of the transmandibular approach to the oral cavity and oropharynx]. / Kritische Aspekte des transmandibulären Zugangswegs zu Mundhöhle und Oropharynx.

BACKGROUND: In the context of tumor surgery, the median mandibulotomy as an access route to the oral cavity and oropharynx provides an excellent overview of the surgical site. However, it is not regarded entirely unproblematic with regard to early and later complications that may arise. OBJECTIVE: The results and complications of the median mandibulotomy will be presented based on data collected from our own patient collective. MATERIALS AND METHODS: A total of 21 patients who had undergone a median mandibulotomy as part of tumor surgery at the Department of Otorhinolaryngology of the SRH Zentralklinikum Suhl were examined over a period from 01 January 2010 to 31 December 2020. The patient files were retrospectively evaluated. RESULTS: A stair-step median mandibulotomy was performed in all 21 patients. Reconstruction was performed using a 2.8 mm thick angled mandibular plate and bicortical locking screws. The mean follow-up period was 29.8 months. In all, 7 patients (33%) had a recurrence at the time of surgery; 5 patients (24%) had already undergone pre-radiation. Furthermore, 18 patients (85.7%) received adjuvant radiotherapy. We found plate loosening or extrusion in 0 of 21 cases. A salivary fistula (4.7%) was observed in 1 patient. Trismus was found in 4 (19%) cases during follow-up. Osteoradionecrosis was found in 2 (9.5%) of 21 cases. Cosmetic deficits were not observed. CONCLUSION: Our results show that the stair-step median mandibulotomy in combination with a 2.8 mm thick reconstruction plate and bicortical locking screws leads to a stable and safe reconstruction even with pre-irradiated situations. Plate loosening or extrusion did not occur.

[Increase of scabies and therapy resistance among German military personnel : An 8-year follow-up study in the Department of Dermatology of the Armed Forces Hospital Berlin, Germany (2012-2019)]. / Anstieg von Skabies und Therapierefraktärität bei Bundeswehrangehörigen : Acht-Jahre-Follow-up-Studie aus der Hautklinik des Bundeswehrkrankenhauses Berlin (2012­2019).

BACKGROUND: The diagnosis of scabies has become surprisingly frequent in Germany in recent years and the use of scabicides has risen significantly. OBJECTIVE: The aim of our survey was to determine whether this trend can also be detected among military personnel of the German Armed Forces (Bundeswehr). METHODS: The study was conducted as a retrospective single-center study over a period of 8 years from 2012 to 2019 in the Department of Dermatology of the Armed Forces Hospital Berlin, Germany. Data were generated from the hospital information system (KIS), which was searched for all scabies-coded diagnoses according to ICD10 code B86 both as outpatients and inpatients. Only first presentations with scabies diagnosis confirmed by dermoscopy or microscopy by a dermatologist were included. Inpatient treatment was required if a patient was not cured after at least three antiscabies treatment cycles in the outpatient setting. RESULTS: The data show that there has been a steady increase in the diagnosis of scabies in Bundeswehr personnel. Moreover, our data show that the number of unsuccessfully treated outpatients increased and required in-hospital treatment. CONCLUSION: We observed an increase of scabies among German military personnel who represent a typical at-risk group. These results support the observations of an increased incidence of scabies in Germany in general and especially in an at-risk population. With the general increase in scabies cases, there are also increasing numbers of German military personnel who are refractory to treatment, which was largely attributed to inadequate treatment of contact persons and individual treatment errors. Nevertheless, the data also emphasize the low overall prevalence of scabies; therefore, all diagnoses should be confirmed by dermoscopy or microscopy after 14 days whenever possible to rule out the bias of overreporting due to false-positive cases diagnosed only by clinical examination.

Plant species affects establishment of Escherichia coli O157:H7 gfp+ on leafy vegetables.

AIMS: Greenhouse trials were conducted with different cultivars of baby leaf spinach, rocket and Swiss chard and inoculation of Escherichia coli O157:H7 gfp+, to determine whether plant species and cultivar have an impact on the establishment of this strain. METHODS AND RESULTS: Three cultivars each of spinach, rocket and Swiss chard were spray inoculated with E. coli O157:H7 gfp+ at doses of log 7 CFU per ml. Due to the different lengths of growing period spinach and Swiss chard were spray inoculated three times and rocket five times, with final inoculation performed 3 days prior to harvest. After a growing period of 26-33 days, E. coli O157:H7 gfp+ was recovered from the leaf surface in mean populations between log 1 and 6 CFU per gram. The lowest occurrence of E. coli O157:H7 gfp+ was found on rocket leaves and the highest on spinach. There was no significant difference in the establishment of E. coli O157:H7 gfp+ between cultivars, but there were differences between plant species. Indigenous phyllosphere bacteria were pure cultured and identified with 16S rRNA gene sequencing. CONCLUSIONS: Despite the same high inoculation dose of E. coli O157:H7 gfp+ on leaves, the establishment rate differed between plant species. However, plant cultivar did not affect establishment. Pantoea agglomerans dominated the identified bacterial isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: As previous studies are inconclusive on choice of model plant species and cultivar, we studied whether plant species or cultivar determines the fate of E. coli O157:H7 gfp+ on leafy vegetables. The findings indicate that plant species is a key determinant in the establishment of E. coli O157:H7 gfp+.

Methods for measurement of root canal curvature: a systematic and critical review.

The assessment of root canal curvature is essential for clinical and research purposes. This systematic review presents an overview of the published techniques for the measurement of root canal curvature features using imaging and to provide a critique of their clinical application. A database search in PubMed, PubMed Central, Embase, Scopus, EBSCO Dentistry & Oral Sciences Source and Virtual Health Library was conducted, using appropriate key words to identify measurement methods for root canal curvatures. The search strategy retrieved 10594 records in total, and 31 records fulfilled the inclusion criteria. From 2D image acquisitions, eleven studies measured exclusively the angle of curvature, an additional thirteen measured other curvature features (level, height, radius, length and shape). Seven reports described methods from 3D imaging (CBCT, µCT). Root canal curvatures should be measured, for clinical proposes, to facilitate endodontic treatment planning, and in research, to reduce the risk of selection bias. This review has revealed that there are many methods described in the literature; however, no consensus exists on which method should be used. Some of the methodologies have potential clinical translation, whereas others are suitable for research purpose only, as they require a specific software or radiographic exposure in the mesiodistal direction.

Defective RNA sensing by RIG-I in severe influenza virus infection.

Influenza virus infection causes worldwide seasonal epidemics. Although influenza is usually a mild disease, a minority of patients experience very severe fulminating disease courses. Previous studies have demonstrated a role for type I interferon (IFN) in anti-viral responses during influenza. So far, however, IFN regulatory factor (IRF)7 deficiency is the only genetic cause of severe influenza described in humans. In this study we present a patient with severe influenza A virus (IAV) H1N1 infection during the 2009 swine flu pandemic. By whole exome sequencing we identified two variants, p.R71H and p.P885S, located in the caspase activation and recruitment domain (CARD) and RNA binding domains, respectively, of DExD/H-box helicase 58 (DDX58) encoding the RNA sensor retinoic acid inducible gene 1 (RIG-I). These variants significantly impair the signalling activity of RIG-I. Similarly, patient cells demonstrate decreased antiviral responses to RIG-I ligands as well as increased proinflammatory responses to IAV, suggesting dysregulation of the innate immune response with increased immunopathology. We suggest that these RIG-I variants may have contributed to severe influenza in this patient and advocate that RIG-I variants should be sought in future studies of genetic factors influencing single-stranded RNA virus infections.

Spatial Distortion of Vibration Modes via Magnetic Correlation of Impurities.

Long wavelength vibrational modes in the ferromagnetic semiconductor Ga_{0.91}Mn_{0.09}As are investigated using time resolved x-ray diffraction. At room temperature, we measure oscillations in the x-ray diffraction intensity corresponding to coherent vibrational modes with well-defined wavelengths. When the correlation of magnetic impurities sets in, we observe the transition of the lattice into a disordered state that does not support coherent modes at large wavelengths. Our measurements point toward a magnetically induced broadening of long wavelength vibrational modes in momentum space and their quasilocalization in the real space. More specifically, long wavelength vibrational modes cannot be assigned to a single wavelength but rather should be represented as a superposition of plane waves with different wavelengths. Our findings have strong implications for the phonon-related processes, especially carrier-phonon and phonon-phonon scattering, which govern the electrical conductivity and thermal management of semiconductor-based devices.

Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight.

The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology to climate science, yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate; visible light scattering provides insufficient resolution; and X-ray synchrotron studies have been limited to ensembles of particles. Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins, vibrational energy transfer by the hydrodynamic interaction of amino acids, and large-scale production of nanoscale structures by flame synthesis.

Association of manual or engine-driven glide path preparation with canal centring and apical transportation: a systematic review.

The role and effect of glide path preparation in root canal treatment remain controversial. This systematic review aims to compare apical transportation and canal centring of different glide path preparation techniques, with or without subsequent engine-driven root canal preparation. A database search in PubMed, PubMed Central, Embase, Scopus, EBSCO Dentistry & Oral Sciences Source and Virtual Health Library was conducted, using appropriate key words to identify the effect of glide path preparation (or its absence) on apical transportation and canal centring. An assessment for the risk of bias in included studies was carried out. Amongst 2146 studies, 18 satisfied the inclusion criteria. Nine studies assessed glide path preparation per se, comparing apical transportation and canal centring of rotary systems and/or manual files; eleven further investigations examined the efficacy of the glide path prior to final canal preparation with different engine-driven systems. Risk of bias and other study design features with potential influence on study outcomes and clinical implications were assessed. Based on the available evidence, and within the limitation of the studies included, preparation of a glide path using rotary sequences performs similarly (in most of the component studies) or significantly better than manual preparation when assessing apical transportation or canal centring. When compared to the absence of a glide path, canal shaping following glide path preparation was of similar, or significantly better quality, in regard to apical transportation or canal centring.

Influence of apical enlargement on the repair of apical periodontitis in rats.

AIM: To evaluate the influence of different apical enlargement protocols on the radiographic and histological healing of apical periodontitis in rats. METHODOLOGY: Apical periodontitis was induced bilaterally in the mandibular right and left first molars of 24 Wistar rats by pulp exposure to the oral cavity for 3 weeks. A standard serial root canal preparation technique was performed in the molar of one side, whilst the opposite side was the control group. Rats were randomly divided into three experimental groups (n = 8), according to the diameter of apical enlargement during root canal preparation: K-files size 20 (EG1), size 25 (EG2) and size 30 (EG3). Each animal was its own positive control, because the opposite arch remained untreated. Root canals were filled with a standard technique. After 3 weeks, the animals were euthanized. The main outcome of apical periodontitis healing was evaluated radiographically (mm2 ) and histologically (ordinal scores of inflammation) using a HE staining technique. The measurement of effect was obtained between the three experimental groups by carrying out generalized estimating equations, with Poisson regression with robust variance, pairing each experimental group with its respective control group within animals, adjusted for the mean within animal differences, with α = 5%. RESULTS: The mean and standard deviations of radiographic apical periodontitis size (mm2 ) and intensity of histological inflammatory scores were, respectively: EG1 (0.44 ± 0.27; 2.25 ± 0.46), EG2 (0.33 ± 0.10; 2.50 ± 0.53) and EG3 (0.22 ± 0.08; 2.63 ± 0.74). After 3 weeks, a significantly more favourable radiographic repair was observed when larger apical enlargement was performed (EG3), compared to EG1 and EG2 (P = 0.001). All experimental groups were associated with a significant difference on the radiographic and histological healing of apical periodontitis compared with its respective control group. CONCLUSION: Under the experimental conditions of this study, a larger apical enlargement protocol favoured a more rapid radiographic repair of apical periodontitis in rats after a 3-week follow-up.

Laboratory Setup for Scanning-Free Grazing Emission X-ray Fluorescence.

Grazing incidence and grazing emission X-ray fluorescence spectroscopy (GI/GE-XRF) are techniques that enable nondestructive, quantitative analysis of elemental depth profiles with a resolution in the nanometer regime. A laboratory setup for soft X-ray GEXRF measurements is presented. Reasonable measurement times could be achieved by combining a highly brilliant laser produced plasma (LPP) source with a scanning-free GEXRF setup, providing a large solid angle of detection. The detector, a pnCCD, was operated in a single photon counting mode in order to utilize its energy dispersive properties. GEXRF profiles of the Ni-Lα,ß line of a nickel-carbon multilayer sample, which displays a lateral (bi)layer thickness gradient, were recorded at several positions. Simulations of theoretical profiles predicted a prominent intensity minimum at grazing emission angles between 5° and 12°, depending strongly on the bilayer thickness of the sample. This information was used to retrieve the bilayer thickness gradient. The results are in good agreement with values obtained by X-ray reflectometry, conventional X-ray fluorescence and transmission electron microscopy measurements and serve as proof-of-principle for the realized GEXRF setup. The presented work demonstrates the potential of nanometer resolved elemental depth profiling in the soft X-ray range with a laboratory source, opening, for example, the possibility of in-line or even in situ process control in semiconductor industry.

Internalization of Escherichia coli O157:H7 gfp+ in rocket and Swiss chard baby leaves as affected by abiotic and biotic damage.

Internalization of human pathogens in edible parts of vegetables eaten raw is a major concern, since once internalized they are protected from sanitizing treatments. In this study, we examined the invasion of gfp-labelled Escherichia coli O157:H7 into intact and biotically (infection with Xanthomonas campestris/Pseudomonas syringae) and abiotically (grating with silicon carbide) damaged leaves of wild rocket (Diplotaxis tenuifolia) and Swiss chard (Beta vulgaris subsp. cicla) using laser scanning confocal microscopy. Bacterial cells were found in internal locations of the tissue, irrespective of tissue health status. Contaminated leaf sections of biotically and abiotically damaged wild rocket leaves showed higher susceptibility to microbial invasion, while the pathogen was internalized in greater numbers into intact Swiss chard leaf sections when abiotically, but not biotically, damaged. The greatest differences were observed between the plant species; after surface sanitization, E. coli O157:H7 was still detected in wild rocket leaves, but not in Swiss chard leaves. SIGNIFICANCE AND IMPACT OF THE STUDY: Contamination of leafy vegetables with Escherichia coli O157:H7 is a growing problem, as reported outbreaks are increasing. However, establishment of this human pathogen in the phyllosphere is not completely understood. Using laser scanning confocal microscopy, we demonstrated that E. coli O157:H7gfp+ can invade plant tissue of Swiss chard and wild rocket leaves and that the bacterium is more sensitive to surface sanitization of Swiss chard leaves. Damage to leaf tissue promoted leaf invasion, but the nature of the damage (abiotic or biotic) and plant species had an impact.

Computational prediction of new CYP17 inhibitors based on pharmacophore modeling, virtual screening and docking approach.

17α-Hydroxylase/C17-20-lyase (P450 17, CYP 17) is an important enzyme in the androgen biosynthesis and inhibitors of this enzyme can be used for the treatment of prostate cancer. With the aim of developing new inhibitors for the target enzyme, we generated a structure-based pharmacophore model to further explain the binding requirements for human CYP17 inhibitors. Seven common features of steroidal CYP17 inhibitors were determined using MOE software. This pharmacophore model was then used to search the Cambridge Structural Database (CSD) with the aim of developing more potent and selective CYP17 inhibitors by identifying new hits. We were able to identify 36 structures as possible active CYP17 inhibitors. Docking studies for the selected compounds from the database were also performed and the best three compounds were chosen as possible hits.

Chemical modification of nucleic acids as a key technology for the development of RNA-based therapeutics.

RNA-based effector molecules (nucleic acid effectors) are important tools in molecular medicine because they offer a strategy to address therapeutically interesting targets that are not "druggable" with classic small molecule inhibitors. However, for in vivo applications, RNA-based effectors require specific chemical modifications to improve their stability and pharmacokinetic properties, as well as to minimize toxic and unspecific off-target effects.

A conserved sugar bridge connected to the WSXWS motif has an important role for transport of IL-21R to the plasma membrane.

Interleukin-21 (IL-21) is a class I cytokine that belongs to the γc-subfamily of cytokines and regulates immune responses. It signals through a heterodimeric receptor complex composed of the IL-21R1 and γc-receptor chains. A characteristic feature of class I cytokine receptors is the presence of a consensus motif WSXWS (WS motif) in the membrane proximal fibronectin type III domain (FNIII) of these receptors. We recently described the structure of the IL-21R:IL-21 complex and showed that the first tryptophan of the WS motif of IL-21R is mannosylated and involved in formation of a sugar bridge that connects the two FNIII domains of the receptor. Furthermore, a mutation within the WS motif of IL-21R was recently shown to cause a novel kind of primary immunodeficiency syndrome (PID). Here, we report the structure of IL-21R alone, which shows that the sugar bridge forms independently of whether IL-21R binds IL-21 or not, and we furthermore investigate the role of this bridge in the export of IL-21R and γC to the plasma membrane. Thus, we provide a molecular explanation for how mutations in the WS motif may cause PIDs.

Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells.

The IFNL4 gene is negatively associated with spontaneous and treatment-induced clearance of hepatitis C virus infection. The activity of IFNλ4 has an important causal role in the pathogenesis, but the molecular details are not fully understood. One possible reason for the detrimental effect of IFNλ4 could be a tissue-specific regulation of an unknown subset of genes. To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. Our data show a surprisingly similar response to all three subtypes of interferon. We also addressed the tissue specificity of the response, and identified a subset of tissue-specific genes. However, the interferon response is robust in both tissues with the majority of the identified genes being regulated in hepatocytes as well as airway epithelial cells. Thus we provide an in-depth analysis of the liver interferon response seen over an array of interferon subtypes and compare it to the response in the lung epithelium.

Steering the azido-tetrazole equilibrium of 4-azidopyrimidines via substituent variation - implications for drug design and azide-alkyne cycloadditions.

This paper focuses on an interesting constitutional isomerism called azido-tetrazole equilibrium which is observed in azido-substituted N-heterocycles. We present a systematic investigation of substituent effects on the isomer ratio within a 2-substituted 4-azidopyrimidine model scaffold. NMR- and IR-spectroscopy as well as X-ray crystallography were employed for thorough analysis and characterization of synthesized derivatives. On the basis of this data, we demonstrate the possibility to steer this valence tautomerism towards the isomer of choice by means of substituent variation. We show that the tetrazole form can act as an efficient disguise for the corresponding azido group masking its well known reactivity in azide-alkyne cycloadditions (ACCs). In copper(I)-catalyzed AAC reactions, substituent-stabilized tetrazoles displayed a highly decreased or even abolished reactivity whereas azides and compounds in the equilibrium were directly converted. By use of an acid sensitive derivative, we provide, to our knowledge, the first experimental basis for a possible exploitation of this dynamic isomerism as a pH-dependent azide-protecting motif for selective SPAAC conjugations in aqueous media. Finally, we demonstrate the applicability and efficiency of stabilized tetrazolo[1,5-c]pyrimidines for Fragment-Based Drug Design (FBDD) in the field of quorum sensing inhibitors.

Small Noncoding 6S RNAs of Bacteria.

Small noncoding RNAs (ncRNAs) are non-translated transcripts with lengths below 300 nucleotide residues. Regulation of cellular processes under the influence of these ncRNAs is the most various in eukaryotic cells, but numerous ncRNAs are also found in bacteria. One of the best-known small prokaryotic ncRNAs is 6S RNA - it has been detected in all branches of bacteria. Due to their conserved secondary structure including a large central "loop" flanked by long double-helical arms, 6S RNAs can bind holoenzymes of RNA polymerase (RNAP) and inhibit their activity. This inhibits transcription of many genes. According to data of comparative transcriptome analysis, the 6S RNA-dependent regulation of transcription affects the expression level of hundreds of genes involved in various cellular processes. 6S RNA has the unique feature of serving as a transcription template for the synthesis of short product RNAs (pRNAs) complementary to the central part of the molecule. The length and abundance of pRNAs vary depending on the physiological status of the cell. The synthesis of pRNAs is of great importance because it releases RNAP and provides reversibility of the inhibition. A similar mechanism has been described for the noncoding mouse B2 RNA that inhibits the activity of RNAP II. This finding can be taken as evidence for the common evolutionary origin of the ncRNA-dependent regulation of RNAP and its immense significance for cells. This review summarizes the state of knowledge about the main features and functions of 6S RNAs from various bacterial species with a special focus on the peculiarities of pRNA synthesis. The majority of functional insights on 6S RNAs have been gained for E. coli 6S RNA as the best-studied model system.

The crystal structure of zebrafish IL-22 reveals an evolutionary, conserved structure highly similar to that of human IL-22.

The class II cytokine family consists of small α-helical signaling proteins including the interleukin-10 (IL-10)/IL-22 family, as well as interferons (IFNs). They regulate the innate immune response and in addition have an important role in protecting epithelial tissues. Teleost fish possess a class II cytokine system surprisingly similar to that of humans, and thus zebrafish offers an attractive model organism for investigating the role of class II cytokines in inflammation. However, the evolution of class II cytokines is critical to understand if we are to take full advantage of zebrafish as a model system. The small size and fast evolution of these cytokines obscure phylogenetic analyses based purely on sequences, but one can overcome this obstacle by using information contained within the structure of those molecules. Here we present the crystal structure of IL-22 from zebrafish (zIL-22) solved at 2.1 Å, which displays a typical class II cytokine architecture. We generated a structure-guided alignment of vertebrate class II cytokines and used it for phylogenetic analysis. Our analysis suggests that IL-22 and IL-26 arose early during the evolution of the IL-10-like cytokines. Thus, we propose an evolutionary scenario of class II cytokines in vertebrates, based on genomic and structural data.