EpiSegMix: a flexible distribution hidden Markov model with duration modeling for chromatin state discovery.

MOTIVATION: Automated chromatin segmentation based on ChIP-seq (chromatin immunoprecipitation followed by sequencing) data reveals insights into the epigenetic regulation of chromatin accessibility. Existing segmentation methods are constrained by simplifying modeling assumptions, which may have a negative impact on the segmentation quality. RESULTS: We introduce EpiSegMix, a novel segmentation method based on a hidden Markov model with flexible read count distribution types and state duration modeling, allowing for a more flexible modeling of both histone signals and segment lengths. In a comparison with existing tools, ChromHMM, Segway, and EpiCSeg, we show that EpiSegMix is more predictive of cell biology, such as gene expression. Its flexible framework enables it to fit an accurate probabilistic model, which has the potential to increase the biological interpretability of chromatin states. AVAILABILITY AND IMPLEMENTATION: Source code: https://gitlab.com/rahmannlab/episegmix.

The jasmonoyl-isoleucine receptor CORONATINE INSENSITIVE1 suppresses defense gene expression in Arabidopsis roots independently of its ligand.

The F-box protein CORONANTINE INSENSITIVE1 (COI1) serves as the receptor for the plant hormone jasmonoyl-isoleucine (JA-Ile). COI1, its co-receptors of the JASMONATE ZIM-domain (JAZ) protein family, and JA-Ile form a functional unit that regulates growth or defense mechanisms in response to various stress cues. Strikingly, COI1, but not JA-Ile, is required for susceptibility of Arabidopsis thaliana towards the soil-borne vascular pathogen Verticillium longisporum. In order to obtain marker genes for further analysis of this JA-Ile-independent COI1 function, transcriptome analysis of roots of coi1 and allene oxide synthase (aos) plants (impaired in JA biosynthesis) was performed. Intriguingly, nearly all of the genes that are differentially expressed in coi1 versus aos and wild type are constitutively more highly expressed in coi1. To support our notion that COI1 acts independently of its known downstream signaling components, coi1 plants were complemented with a COI1 variant (COI1AA ) that is compromised in its interaction with JAZs. As expected, these plants showed only weak induction of the expression of the JA-Ile marker gene VEGETATIVE STORAGE PROTEIN2 after wounding and remained sterile. On the other hand, genes affected by COI1 but not by JA-Ile were still strongly repressed by COI1AA . We suggest that COI1 has a potential moonlighting function that serves to repress gene expression in a JA-Ile- and JAZ-independent manner.

Disinfection of Transvaginal Ultrasound Probes by Ultraviolet C - A clinical Evaluation of Automated and Manual Reprocessing Methods.

PURPOSE: Since pathogens can be transmitted to patients via transvaginal ultrasound probes, it is of particular importance that cleaning and disinfection are performed adequately. This study was designed to do a qualitative comparison of a low-level disinfection technique with disinfectant-impregnated wipes and an automated disinfection technique using ultraviolet C radiation in a clinical setting. MATERIALS AND METHODS: The transvaginal ultrasound probes used in two groups of 160 patients were compared in a prospective controlled study regarding the effectiveness of manual low-level disinfection (Mikrozid sensitive wipes) and automated disinfection using ultraviolet C radiation (Antigermix AS1). Microbiological samples were taken from the whole surface of the probe before and after the disinfection process. RESULTS: Before disinfection, 98.75 % (316/320) of the samples showed bacterial contamination. After automated and manual disinfection, the contamination rates were 34.2 % (54/158, automated) and 40.5 % (64/158, disinfectant wipes) (p > 0.05). Pathogens with the potential to cause healthcare-associated infections, such as Enterococcus faecalis and Klebsiella pneumoniae, were removed completely by both techniques. Manual disinfection showed a lower contamination rate after disinfection of bacteria that usually belong to the vaginal, pharyngeal and skin flora (disinfectant wipes 10.6 %, 11/104, automated 32.5 %, 38/117) (p < 0.001). CONCLUSION: For the clinical routine, automated disinfection with ultraviolet C is a promising technique for transvaginal ultrasound probes because of the simple handling and time efficiency. In our study, this method was completely effective against nosocomial pathogens. However, the study didn't show any significant difference in terms of effectiveness compared to low-level wipe disinfection.

[Pre- and perinatal risk factors in autism spectrum disorder and attention deficit/hyperactivity disorder]. / Prä- und perinatale Risikofaktoren bei Autismus-Spektrum-Störung und Aktivitäts- und Aufmerksamkeitsstörung.

Objective: Epidemiological studies indicate the relevance of pre- and perinatal risk factors for the genesis of attention deficit/hyperactivity disorder and autism spectrum disorder. This study compares potential risk factors in a clinical sample of children with ADHD, ASD, the combination of both diseases, ADHD and oppositional defiant or conduct disorder (ADHD & ODD/CD) and examined whether the existence of additional risk factors promotes the occurrence of combined diseases. Method: We compared the pre- and perinatal risk factors of 341 patients (299 boys, 42 girls) from a clinical population, differentiating between children with ADHD (n=80), ASD (n=122), ADHD & ASD (n=55), or ADHD & ODD/CD (n=84). Results: We observed a higher rate of maternal smoking, a higher rate of migration, and lower parental education among the children with ADHD & ODD/CD compared to those with ASD or ADHD. The rate of migration background was higher among the children with ASD compared to children with ADHD. Miscarriage was a specific risk factor for ADHD & ASD. Conclusion: Numerous risk factors described in epidemiological studies occurred only rarely in our clinical sample. The distribution of most risk factors was comparable between the examined diseases.

Membrane protein interactions between different Arabidopsis thaliana MRS2-type magnesium transporters are highly permissive.

Membrane proteins of the Arabidopsis thaliana MRS2 (MGT) family have been characterised as magnesium transporters. Like their bacterial CorA homologues, the plant MRS2 proteins are characterised by an invariable GMN tripeptide motif terminating the first of two closely spaced transmembrane domains at the carboxy-termini. The functional Mg(2+) transport channel is assembled as a pentamer in the case of CorA. However, in contrast to the single CorA genes of bacteria, plant genomes encode up to 10 highly divergent MRS2 proteins. To elucidate structure-function relationships and the possibility of plant MRS2 hetero-pentamer formation, we performed protein-protein interaction studies in the yeast mating-based split-ubiquitin system (mbSUS) and concomitant protein modelling using I-TASSER. Despite very restricted sequence similarities and variable polypeptide insertions all AtMRS2 proteins feature the key structural elements determined for the CorA crystal structure. The mbSUS setup conclusively demonstrates protein-protein interactions of any given AtMRS2 protein not only with itself but also highly permissive interactions to varying degrees among all AtMRS2 proteins. AtMRS2-3 seems particularly prone to non-selective, strong interactions with the other homologues. Deletion constructs show that six amino acids may be deleted from the carboxy-terminus and 27 (but not 41) from the amino-terminus of AtMRS2-7 without impairment of homologous or heterologous protein interactions. Despite significant diversification, the plant MRS2 proteins have obviously retained an ancient CorA/MRS2 core structure and the capacity for protein-protein interactions. Plant magnesium homeostasis may be influenced by hetero-oligomer channel formation where different plant MRS2 proteins meet in the same membrane naturally or in transgenic approaches.

Dental MRI-only a future vision or standard of care? A literature review on current indications and applications of MRI in dentistry.

MRI is increasingly used as a diagnostic tool for visualising the dentoalveolar complex. A comprehensive review of the current indications and applications of MRI in the dental specialities of orthodontics (I), endodontics (II), prosthodontics (III), periodontics (IV), and oral surgery (V), pediatric dentistry (VI), operative dentistry is still missing and is therefore provided by the present work.The current literature on dental MRI shows that it is used for cephalometry in orthodontics and dentofacial orthopaedics, detection of dental pulp inflammation, characterisation of periapical and marginal periodontal pathologies of teeth, caries detection, and identification of the inferior alveolar nerve, impacted teeth and dentofacial anatomy for dental implant planning, respectively. Specific protocols regarding the miniature anatomy of the dentofacial complex, the presence of hard tissues, and foreign body restorations are used along with dedicated coils for the improved image quality of the facial skull.Dental MRI poses a clinically useful radiation-free imaging tool for visualising the dentoalveolar complex across dental specialities when respecting the indications and limitations.

T cells of colorectal cancer patients' stimulated by neoantigenic and cryptic peptides better recognize autologous tumor cells.

BACKGROUND: Patients with cancers that exhibit extraordinarily high somatic mutation numbers are ideal candidates for immunotherapy and enable identifying tumor-specific peptides through stimulation of tumor-reactive T cells (Tc). METHODS: Colorectal cancers (CRC) HROC113 and HROC285 were selected based on high TMB, microsatellite instability and HLA class I expression. Their HLA ligandome was characterized using mass spectrometry, compared with the HLA ligand atlas and HLA class I-binding affinity was predicted. Cryptic peptides were identified using Peptide-PRISM. Patients' Tc were isolated from either peripheral blood (pTc) or tumor material (tumor-infiltrating Tc, TiTc) and expanded. In addition, B-lymphoblastoid cells (B-LCL) were generated and used as antigen-presenting cells. pTc and TiTc were stimulated twice for 7 days using peptide pool-loaded B-LCL. Subsequently, interferon gamma (IFNγ) release was quantified by ELISpot. Finally, cytotoxicity against autologous tumor cells was assessed in a degranulation assay. RESULTS: 100 tumor-specific candidate peptides-97 cryptic peptides and 3 classically mutated neoantigens-were selected. The neoantigens originated from single nucleotide substitutions in the genes IQGAP1, CTNNB1, and TRIT1. Cryptic and neoantigenic peptides inducing IFNγ secretion of Tc were further investigated. Stimulation of pTc and TiTc with neoantigens and selected cryptic peptides resulted in increased release of cytotoxic granules in the presence of autologous tumor cells, substantiating their improved tumor cell recognition. Tetramer staining showed an enhanced number of pTc and TiTc specific for the IQGAP1 neoantigen. Subpopulation analysis prior to peptide stimulation revealed that pTc mainly consisted of memory Tc, whereas TiTc constituted primarily of effector and effector memory Tc. This allows to infer that TiTc reacting to neoantigens and cryptic peptides must be present within the tumor microenvironment. CONCLUSION: These results prove that the analyzed CRC present both mutated neoantigenic and cryptic peptides on their HLA class I molecules. Moreover, stimulation with these peptides significantly strengthened tumor cell recognition by Tc. Since the overall number of neoantigenic peptides identifiable by HLA ligandome analysis hitherto is small, our data emphasize the relevance of increasing the target scope for cancer vaccines by the cryptic peptide category.

Molecular identification of forensically important blowfly species (Diptera: Calliphoridae) from Germany.

Forensic entomology applies knowledge about the behaviour and ecology of insects associated to corpses to homicide investigations. It is possible to calculate a minimum post-mortem interval by determining the age of the oldest blowfly larvae feeding on a corpse. The growth rate of the larvae is highly dependent on temperature and also varies between the different blowfly species infesting a corpse. It is, thus, crucial to correctly identify the species collected from a crime scene. To increase the quality of species identification, molecular methods were applied to 53 individuals of six different species sampled in Bonn, Germany: Calliphora vicina, Calliphora vomitoria, Lucilia caesar, Lucilia sericata, Lucilia illustris, and Protophormia terraenovae. We extracted DNA and checked a 229 bp sequence within the mitochondrial cytochrome oxidase subunit I. The sequences of the local flies were aligned to published data of specimens from other countries. We also studied the practical value of the analysed DNA region for their differentiation. All species were matched correctly by a Basic Local Alignment Search Tool (BLAST) search apart from L. caesar and L. illustris. Although molecular methods are very useful-especially if it is necessary to identify small fragments of insect material or very young larvae-we propose to use it only in addition to the conventional methods.