Genome information management and integrated data analysis with HaloLex

HaloLex is a software system for the central management, integration, curation, and web-based visualization of genomic and other -omics data for any given microorganism. The system has been employed for the manual curation of three haloarchaeal genomes, namely Halobacterium salinarum (strain R1), Natronomonas pharaonis, and Haloquadratum walsbyi. HaloLex, in particular, enables the integrated analysis of genome-wide proteomic results with the underlying genomic data. This has proven indispensable to generate reliable gene predictions for GC-rich genomes, which, due to their characteristically low abundance of stop codons, are known to be hard targets for standard gene finders, especially concerning start codon assignment. The proteomic identification of more than 600 N-terminal peptides has greatly increased the reliability of the start codon assignment for Halobacterium salinarum. Application of homology-based methods to the published genome of Haloarcula marismortui allowed to detect 47 previously unidentified genes (a problem that is particularly serious for short protein sequences) and to correct more than 300 start codon misassignments

Haloquadratum walsbyi : Limited Diversity in a Global Pond

BACKGROUND: Haloquadratum walsbyi commonly dominates the microbial flora of hypersaline waters. Its cells are extremely fragile squares requiring >14%(w/v) salt for growth, properties that should limit its dispersal and promote geographical isolation and divergence. To assess this, the genome sequences of two isolates recovered from sites at near maximum distance on Earth, were compared. PRINCIPAL FINDINGS: Both chromosomes are 3.1 MB in size, and 84% of each sequence was highly similar to the other (98.6% identity), comprising the core sequence. ORFs of this shared sequence were completely synteneic (conserved in genomic orientation and order), without inversion or rearrangement. Strain-specific insertions/deletions could be precisely mapped, often allowing the genetic events to be inferred. Many inferred deletions were associated with short direct repeats (4-20 bp). Deletion-coupled insertions are frequent, producing different sequences at identical positions. In cases where the inserted and deleted sequences are homologous, this leads to variant genes in a common synteneic background (as already described by others). Cas/CRISPR systems are present in C23(T) but have been lost in HBSQ001 except for a few spacer remnants. Numerous types of mobile genetic elements occur in both strains, most of which appear to be active, and with some specifically targetting others. Strain C23(T) carries two ∼6 kb plasmids that show similarity to halovirus His1 and to sequences nearby halovirus/plasmid gene clusters commonly found in haloarchaea. CONCLUSIONS: Deletion-coupled insertions show that Hqr. walsbyi evolves by uptake and precise integration of foreign DNA, probably originating from close relatives. Change is also driven by mobile genetic elements but these do not by themselves explain the atypically low gene coding density found in this species. The remarkable genome conservation despite the presence of active systems for genome rearrangement implies both an efficient global dispersal system, and a high selective fitness for this species

MIPSPlantsDB—plant database resource for integrative and comparative plant genome research

Genome-oriented plant research delivers rapidly increasing amount of plant genome data. Comprehensive and structured information resources are required to structure and communicate genome and associated analytical data for model organisms as well as for crops. The increase in available plant genomic data enables powerful comparative analysis and integrative approaches. PlantsDB aims to provide data and information resources for individual plant species and in addition to build a platform for integrative and comparative plant genome research. PlantsDB is constituted from genome databases for Arabidopsis, Medicago, Lotus, rice, maize and tomato. Complementary data resources for cis elements, repetive elements and extensive cross-species comparisons are implemented. The PlantsDB portal can be reached at

Die archäologischen Untersuchungen 2016–2021 in Ascoli Satriano/Giarnera Piccola (Prov. Foggia/Apulien)

Recent archaeological investigations at Ascoli Satriano have shed new light on the pre-Roman occupation of northern Apulia (ancient Daunia). The findings document a long-term and locally consistent attachment to the core site of Giarnera Piccola from the 8th to the late 4th century BCE. A close relationship is discerned, both in time and space, of architectural structures and burials. The new local discoveries testify to the existence of this situation from the earliest hut structures onwards and show its persistence until the place’s abandonment. While the detection of new fragments of two Daunian stelae in a shaft/well points to early burial activities, the character of the entangled relationship still has to be scrutinized. Archaeometric and scientific analyses furthermore attest to activities in agriculture and in pottery production

Aktuelle Herausforderungen in der Therapie des Typ-1-Diabetes beim Kind

Das 1921 entdeckte Insulin wurde 1922 erstmals als Therapie für Typ-1-Diabetes eingeführt. Hundert Jahre später wird es immer noch als einzige medikamentöse Behandlung eingesetzt. Die jüngsten Fortschritte haben zu einer erheblichen Optimierung der Stoffwechselkontrolle beigetragen. Einleitung Typ-1-Diabetes (T1D) ist eine der häufigsten chronischen Erkrankungen bei Kindern, mit einer jährlichen Inzidenzzunahme von 3% [1]. Die Ätiologie des T1D ist unbekannt, aber eine Dysregulation der Autoimmunität, dokumentiert durch die Zirkulation von Autoantikörpern, sowie eine genetische Prädisposition sind ursächlich beteiligt. Das Risiko, an T1D zu erkranken, beträgt bei Kindern 0,4%; gibt es bereits an T1D-erkrankte Familienangehörige, steigt das Risiko um das Zehnfache. Neueste Daten weisen auf einen deutlichen Anstieg der weltweiten Inzidenz während der Corona-Pandemie hin [2–5]. Ziel dieses Beitrags ist es, die neuesten Entwicklungen und aktuellen Herausforderungen bei der Behandlung des T1D bei Kindern darzustellen

Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest

Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation

Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction.

Endothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network

Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.

Human in vitro generated monocyte-derived dendritic cells (moDCs) and macrophages are used clinically, e.g., to induce immunity against cancer. However, their physiological counterparts, ontogeny, transcriptional regulation, and heterogeneity remains largely unknown, hampering their clinical use. High-dimensional techniques were used to elucidate transcriptional, phenotypic, and functional differences between human in vivo and in vitro generated mononuclear phagocytes to facilitate their full potential in the clinic. We demonstrate that monocytes differentiated by macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) resembled in vivo inflammatory macrophages, while moDCs resembled in vivo inflammatory DCs. Moreover, differentiated monocytes presented with profound transcriptomic, phenotypic, and functional differences. Monocytes integrated GM-CSF and IL-4 stimulation combinatorically and temporally, resulting in a mode- and time-dependent differentiation relying on NCOR2. Finally, moDCs are phenotypically heterogeneous and therefore necessitate the use of high-dimensional phenotyping to open new possibilities for better clinical tailoring of these cellular therapies

Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest

Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation

Framework and baseline examination of the German National Cohort (NAKO)

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5