altAFplotter: a web app for reliable UPD detection in NGS diagnostics.

Background: The detection of uniparental disomies (the inheritance of both chromosome homologues from a single parent, UPDs) is not part of most standard or commercial NGS-pipelines in human genetics and thus a common gap in NGS diagnostics. To address this we developed a tool for UPD-detection based on panel or exome data which is easy to use and publicly available.

Results: The app is freely available at https://altafplotter.

Automatized detection of uniparental disomies in a large cohort.

Uniparental disomy (UPD) is the inheritance of both homologues of a chromosome from only one parent. The detection of UPDs in sequencing data is not well established and a common gap in genetic diagnostics. We applied our in-house UPD detection pipeline to evaluate a cohort of 9212 samples, including multigene panels as well as exome sequencing data in a single, duo or trio constellation.

Case report: Complete paternal isodisomy on chromosome 18 induces methylation changes in promotor in a case with arthrogryposis.

Uniparental disomy (UPD) is the inheritance of both alleles of a chromosome from only one parent. So far, the detection of UPDs in sequencing data is not well established and a known gap in next-generation sequencing (NGS) diagnostics. By developing a new tool for UPD detection, we re-evaluated an eight-year-old individual presenting with scoliosis, muscle weakness and global developmental delay.

Aerosol-Radiation Interactions in China in Winter: Competing Effects of Reduced Shortwave Radiation and Cloud-Snowfall-Albedo Feedbacks Under Rapidly Changing Emissions.

Since 2013, Chinese policies have dramatically reduced emissions of particulates and their gas-phase precursors, but the implications of these reductions for aerosol-radiation interactions are unknown. Using a global, coupled chemistry-climate model, we examine how the radiative impacts of Chinese air pollution in the winter months of 2012 and 2013 affect local meteorology and how these changes may, in turn, influence surface concentrations of PM, particulate matter with diameter <2.5 μm.

Catalytic role of formaldehyde in particulate matter formation.

Formaldehyde (HCHO), the simplest and most abundant carbonyl in the atmosphere, contributes to particulate matter (PM) formation via two in-cloud processing pathways. First, in a catalytic pathway, HCHO reacts with hydrogen peroxide (HO) to form hydroxymethyl hydroperoxide (HMHP), which rapidly oxidizes dissolved sulfur dioxide (SO) to sulfate, regenerating HCHO. Second, HCHO reacts with dissolved SO to form hydroxymethanesulfonate (HMS), which upon oxidation with the hydroxyl radical (OH) forms sulfate and also reforms HCHO.

Global Importance of Hydroxymethanesulfonate in Ambient Particulate Matter: Implications for Air Quality.

Sulfur compounds are an important constituent of particulate matter, with impacts on climate and public health. While most sulfur observed in particulate matter has been assumed to be sulfate, laboratory experiments reveal that hydroxymethanesulfonate (HMS), an adduct formed by aqueous phase chemical reaction of dissolved HCHO and SO, may be easily misinterpreted in measurements as sulfate. Here we present observational and modeling evidence for a ubiquitous global presence of HMS.

An intrinsic oscillator drives the blood stage cycle of the malaria parasite .

The blood stage of the infection of the malaria parasite exhibits a 48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, which triggers 48-hour fever cycles in the host. This cycle could be driven extrinsically by host circadian processes or by a parasite-intrinsic oscillator. To distinguish between these hypotheses, we examine the cycle in an in vitro culture system and show that the parasite has molecular signatures associated with circadian and cell cycle oscillators.

Novel malaria antigen Plasmodium yoelii E140 induces antibody-mediated sterile protection in mice against malaria challenge.

Only a small fraction of the antigens expressed by malaria parasites have been evaluated as vaccine candidates. A successful malaria subunit vaccine will likely require multiple antigenic targets to achieve broad protection with high protective efficacy. Here we describe protective efficacy of a novel antigen, Plasmodium yoelii (Py) E140 (PyE140), evaluated against P.

Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach.

The symptoms of malaria are brought about by blood-stage parasites, which are established when merozoites invade human erythrocytes. Our understanding of the molecular events that underpin erythrocyte invasion remains hampered by the short-period of time that merozoites are invasive. To address this challenge, a Plasmodium falciparum gamma-irradiated long-lived merozoite (LLM) line was developed and investigated.

A critical survey of vestigial structures in the postcranial skeletons of extant mammals.

In the Mammalia, vestigial skeletal structures abound but have not previously been the focus of study, with a few exceptions (e.g., whale pelves).

Exogenous Salicylic Acid Enhances the Resistance of Wheat Seedlings to Hessian Fly (Diptera: Cecidomyiidae) Infestation Under Heat Stress.

Heat stress exerts significant impact on plant-parasite interactions. Phytohormones, such as salicylic acid (SA), play important roles in plant defense against parasite attacks. Here, we studied the impact of a combination of heat stress and exogenous SA on the resistance of wheat (Triticum aestivum L.

Transient heat stress compromises the resistance of wheat (Poales: Poaceae) seedlings to Hessian fly (Diptera: Cecidomyiidae) infestation.

Heat stress exerts a profound impact on the resistance of plants to parasites. In this research, we investigated the impact of an acute transient heat stress on the resistance of the wheat line 'Molly,' which contains the R gene H13, to an avirulent Hessian fly (Mayetiola destructor (Say)) population. We found that a significant portion of Molly seedlings stressed at 40 degrees C for 6 h during or after the initial Hessian fly larval attack became susceptible to otherwise avirulent insects, whereas unstressed control plants remained 100% resistant.

Overcoming antigenic diversity by enhancing the immunogenicity of conserved epitopes on the malaria vaccine candidate apical membrane antigen-1.

Malaria vaccine candidate Apical Membrane Antigen-1 (AMA1) induces protection, but only against parasite strains that are closely related to the vaccine. Overcoming the AMA1 diversity problem will require an understanding of the structural basis of cross-strain invasion inhibition. A vaccine containing four diverse allelic proteins 3D7, FVO, HB3 and W2mef (AMA1 Quadvax or QV) elicited polyclonal rabbit antibodies that similarly inhibited the invasion of four vaccine and 22 non-vaccine strains of P.

Actin cytoskeleton and organelle movement in the sporangiophore of the zygomycete Phycomyces blakesleeanus.

Growth, photo- and gravitropism of sporangiophores of the zygomycete Phycomyces blakesleeanus occur within the apical growing zone, a cylindrical structure (diameter about 100 μm) that reaches about 1.5-2.5 mm below the tip and has growth rates up to 50 μm·min(-1) .

Disrupting malaria parasite AMA1-RON2 interaction with a small molecule prevents erythrocyte invasion.

Plasmodium falciparum resistance to artemisinin derivatives, the first-line antimalarial drug, drives the search for new classes of chemotherapeutic agents. Current discovery is primarily directed against the intracellular forms of the parasite. However, late schizont-infected red blood cells (RBCs) may still rupture and cause disease by sequestration; consequently targeting invasion may reduce disease severity.

Impact of dietary manganese concentration on status criteria to determine manganese requirement in piglets.

The Mn requirement for pigs is not well established. This study aimed to find criteria for assessing growing piglet supply status for Mn and to determine whether the current Mn recommendations meet the requirements for piglets. Thirty-six weaned male castrated 27-day-old piglets (7.

Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers commitment to invasion.

The commitment of Plasmodium merozoites to invade red blood cells (RBCs) is marked by the formation of a junction between the merozoite and the RBC and the coordinated induction of the parasitophorous vacuole. Despite its importance, the molecular events underlying the parasite's commitment to invasion are not well understood. Here we show that the interaction of two parasite proteins, RON2 and AMA1, known to be critical for invasion, is essential to trigger junction formation.

Delineation of stage specific expression of Plasmodium falciparum EBA-175 by biologically functional region II monoclonal antibodies.

Background: The malaria parasite Plasmodium falciparum EBA-175 binds its receptor sialic acids on glycophorin A when invading erythrocytes. The receptor-binding region (RII) contains two cysteine-rich domains with similar cysteine motifs (F1 and F2). Functional relationships between F1 and F2 domains and characterization of EBA-175 were studied using specific monoclonal antibodies (mAbs) against these domains.

Plasmodium falciparum field isolates use complement receptor 1 (CR1) as a receptor for invasion of erythrocytes.

A majority of Plasmodium falciparum strains invade erythrocytes through interactions with sialic acid (SA) on glycophorins. However, we recently reported that complement receptor 1 (CR1) is a SA-independent invasion receptor of many laboratory strains of P. falciparum.

Multiple antigen peptide vaccines against Plasmodium falciparum malaria.

The multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis, and immunogenicity of three Plasmodium falciparum MAP vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. Antibody and cellular responses were determined in three inbred (C57BL/6, BALB/c, and A/J) strains, one congenic (HLA-A2 on the C57BL/6 background) strain, and one outbred strain (CD1) of mice.

Complement receptor 1 is a sialic acid-independent erythrocyte receptor of Plasmodium falciparum.

Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood.

Feeding a ROS-generator to Caenorhabditis elegans leads to increased expression of small heat shock protein HSP-16.2 and hormesis.

Reactive oxygen species (ROS) are thought to be a driving force in the aging process. In transgenic Caenorhabditis elegans expressing green fluorescent protein (GFP) under control of the hsp-16.2 promoter (CL2070) 100 muM of the ROS-generator juglone induced GFP-expression.

Centrins, cell cycle regulation proteins in human malaria parasite Plasmodium falciparum.

Molecules and cellular mechanisms that regulate the process of cell division in malaria parasites remain poorly understood. In this study we isolate and characterize the four Plasmodium falciparum centrins (PfCENs) and, by growth complementation studies, provide evidence for their involvement in cell division. Centrins are cytoskeleton proteins with key roles in cell division, including centrosome duplication, and possess four Ca(2+)-binding EF hand domains.

Molecular factors and biochemical pathways induced by febrile temperature in intraerythrocytic Plasmodium falciparum parasites.

Intermittent episodes of febrile illness are the most benign and recognized symptom of infection with malaria parasites, although the effects on parasite survival and virulence remain unclear. In this study, we identified the molecular factors altered in response to febrile temperature by measuring differential expression levels of individual genes using high-density oligonucleotide microarray technology and by performing biological assays in asexual-stage Plasmodium falciparum parasite cultures incubated at 37 degrees C and 41 degrees C (an elevated temperature that is equivalent to malaria-induced febrile illness in the host). Elevated temperature had a profound influence on expression of individual genes; 336 of approximately 5,300 genes (6.

Protein disulfide isomerase assisted protein folding in malaria parasites.

In eukaryotes, the formation of protein disulfide bonds among cysteine residues is mediated by protein disulfide isomerases and occurs in the highly oxidised environment of the endoplasmic reticulum. This process is poorly understood in malaria parasites. In this paper, we report the gene isolation, sequence and phylogenetic comparisons, protein structure and thioredoxin-domain analyses of nine protein disulfide isomerases-like molecules from five species of malaria parasites including Plasmodium falciparum and Plasmodium vivax (human), Plasmodium knowlesi (simian) and Plasmodium berghei and Plasmodium yoelii (murine).