Automated Test Assembly in R: The eatATA Package

Combining items from an item pool into test forms (test assembly) is a frequent task in psychological and educational testing. Although efficient methods for automated test assembly exist, these are often unknown or unavailable to practitioners. In this paper we present the R package eatATA, which allows using several mixed-integer programming solvers for automated test assembly in R. We describe the general functionality and the common work flow of eatATA using a minimal example. We also provide four more elaborate use cases of automated test assembly: (a) The assembly of multiple test forms for a pilot study; (b) the assembly of blocks of items for a multiple matrix booklet design in the context of a large-scale assessment; (c) the assembly of two linear test forms for individual diagnostic purposes; (d) the assembly of multi-stage testing modules for individual diagnostic purposes. All use cases are accompanied with example item pools and commented R code.Peer Reviewe

Risks of pyrrolizidine alkaloids in tea and herbal infusions

Pyrrolizidinalkaloide (PA) sind sekundäre Pflanzeninhaltsstoffe, die von einer Vielzahl von Pflanzen gebildet werden und u. a. zur Abwehr von Fraßfeinden dienen. Toxikologisch bedeutsam sind die PA, die eine Doppelbindung in 1,2-Position aufweisen. Diese können zu gesundheitlichen Schäden bei Mensch und Tier führen, wobei die Leber das Hauptzielorgan darstellt. Neben den bekannten hepatotoxischen Effekten können 1,2-ungesättigte PA auch die DNA schädigen und krebserzeugend wirken. Die Verbindungen gelangen in erster Linie über Wild- und Beikräuter in die Lebensmittelkette. In der im Jahr 2016 durch das Bundes­institut für Risikobewertung (BfR) veröffentlichten Bewertung stellte der Verzehr von kontaminiertem Tee und Kräutertee die wesentliche Expositionsquelle für die Bevölkerung gegenüber 1,2-ungesättigten PA in Deutschland dar; aber auch andere Lebensmittel können zur Aufnahme beitragen. In der vorliegenden Arbeit, in der ausschließlich Tee und Kräutertee berücksichtigt werden, zeigt sich, dass die Gehalte an 1,2-ungesättigten PA in dieser Lebensmittelgruppe im Vergleich zu 2016 deutlich gesunken sind. Dennoch kann es insbesondere bei Personen, die langfristig hohe Mengen Kräutertee bzw. Rooibostee verzehren, auch gegenwärtig noch zu Aufnahmemengen kommen, die in einem Margin of Exposure von unter 10.000 resultieren, weshalb es auch weiterhin angezeigt scheint, Maßnahmen zur Senkung der Gehalte durchzuführen.Pyrrolizidine alkaloids (PA) are secondary plant metabolites which are produced by a large number of plants, e. g. to ward off herbivores. PA with a double bond in the 1,2-position are of toxicological relevance. These derivatives can cause adverse health effects in humans and animals, with the liver being the major target organ. Besides the known hepatotoxic effects, 1,2-unsaturated PA may also damage DNA and may be carcinogenic. The occurrence of these compounds in foods is primarily caused by contamination with wild herbs. In the assessment published in 2016 by the German Federal Institute for Risk Assessment (BfR), consumption of contaminated tea and herbal tea was the main source of exposure for the population to 1.2-unsaturated PA in Germany; however, other foods can also contribute to intake. The present study, which focuses exclusively on tea and herbal tea, shows that levels of 1,2-unsaturated PA in this food group have decreased significantly compared to 2016. Nevertheless, persons who consume high amounts of herbal tea or rooibos tea in the long term may still be exposed to intakes that result in a margin of exposure of less than 10,000, which is why it still seems appropriate to implement measures to reduce the levels

AUREOCHROME1a-mediated induction of the diatom-specific cyclin dsCYC2 controls the onset of cell division in diatoms (Phaeodactylum tricornutum)

Cell division in photosynthetic organisms is tightly regulated by light. Although the light dependency of the onset of the cell cycle has been well characterized in various phototrophs, little is known about the cellular signaling cascades connecting light perception to cell cycle activation and progression. Here, we demonstrate that diatom-specific cyclin 2 (dsCYC2) in Phaeodactylum tricornutum displays a transcriptional peak within 15 min after light exposure, long before the onset of cell division. The product of dsCYC2 binds to the cyclin-dependent kinase CDKA1 and can complement G1 cyclin-deficient yeast. Consistent with the role of dsCYC2 in controlling a G1-to-S light-dependent cell cycle checkpoint, dsCYC2 silencing decreases the rate of cell division in diatoms exposed to light-dark cycles but not to constant light. Transcriptional induction of dsCYC2 is triggered by blue light in a fluence rate-dependent manner. Consistent with this, dsCYC2 is a transcriptional target of the blue light sensor AUREOCHROME1a, which functions synergistically with the basic leucine zipper (bZIP) transcription factor bZIP10 to induce dsCYC2 transcription. The functional characterization of a cyclin whose transcription is controlled by light and whose activity connects light signaling to cell cycle progression contributes significantly to our understanding of the molecular mechanisms underlying light-dependent cell cycle onset in diatoms

Yaws Disease Caused by Treponema pallidum subspecies pertenue in Wild Chimpanzee, Guinea, 2019

Yaws-like lesions are widely reported in wild African great apes, yet the causative agent has not been confirmed in affected animals. We describe yaws-like lesions in a wild chimpanzee in Guinea for which we demonstrate infection with Treponema pallidum subsp. pertenue. Assessing the conservation implications of this pathogen requires further research

NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62

NEMO is a ubiquitin-binding protein which regulates canonical NF-kappa B pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-kappa B-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges. Moreover, a patient with a mutation in the NEMO-encoding IKBKG gene resulting in defective binding of NEMO to linear ubiquitin chains, developed a widespread mixed brain proteinopathy, including alpha-synuclein, tau and TDP-43 pathology. NEMO amplifies linear ubiquitylation at alpha-synuclein aggregates and promotes the local concentration of p62 into foci. In vitro, NEMO lowers the threshold concentrations required for ubiquitin-dependent phase transition of p62. In summary, NEMO reshapes the aggregate surface for efficient autophagosomal clearance by providing a mobile phase at the aggregate interphase favoring co-condensation with p62. Selective autophagy helps to degrade aggregated proteins accumulating in neurodegenerative diseases. Here, the authors show that NEMO, a ubiquitin binding protein previously linked to innate immune signaling, is recruited to misfolded proteins and promotes their autophagic clearance by forming condensates with the autophagy receptor p62

Local Application of BMP-2 Specific Plasmids in Fibrin Glue does not Promote Implant Fixation

<p>Abstract</p> <p>Background</p> <p>BMP-2 is known to accelerate fracture healing and might also enhance osseointegration and implant fixation. Application of recombinant BMP-2 has a time-limited effect. Therefore, a gene transfer approach with a steady production of BMP-2 appears to be attractive. The aim of this study was to examine the effect of locally applied BMP-2 plasmids on the bone-implant integration in a non-weight bearing rabbit tibia model using a comparatively new non-viral copolymer-protected gene vector (COPROG).</p> <p>Methods</p> <p>Sixty rabbits were divided into 4 groups. All of them received nailing of both tibiae. The verum group had the nails inserted with the COPROG vector and BMP-2 plasmids using fibrin glue as a carrier. Controls were a group with fibrin glue only and a blank group. After 28 and 56 days, these three groups were sacrificed and one tibia was randomly chosen for biomechanical testing, while the other tibia underwent histomorphometrical examination. In a fourth group, a reporter-gene was incorporated in the fibrin glue instead of the BMP-2 formula to prove that transfection was successful.</p> <p>Results</p> <p>Implant fixation strength was significantly lower after 28 and 56 days in the verum group. Histomorphometry supported the findings after 28 days, showing less bone-implant contact.</p> <p>In the fourth group, successful transfection could be confirmed by detection of the reporter-gene in 20 of 22 tibiae. But, also systemic reporter-gene expression was found in heterotopic locations, showing an undesired spreading of the locally applied gene formula.</p> <p>Conclusion</p> <p>Our results underline the transfecting capability of this vector and support the idea that BMP-2 might diminish osseointegration. Further studies are necessary to specify the exact mechanisms and the systemic effects.</p

Membrane potential and Ca2+ concentration dependence on pressure and vasoactive agents in arterial smooth muscle: A model

Arterial smooth muscle (SM) cells respond autonomously to changes in intravascular pressure, adjusting tension to maintain vessel diameter. The values of membrane potential (V_m) and sarcoplasmic Ca^2+ concentration (Ca_in) within minutes of a change in pressure are the results of two opposing pathways, both of which use Ca^2+ as a signal. This works because the two Ca^2+-signaling pathways are confined to distinct microdomains in which the Ca^2+ concentrations needed to activate key channels are transiently higher than Cain. A mathematical model of an isolated arterial SM cell is presented that incorporates the two types of microdomains. The first type consists of junctions between cisternae of the peripheral sarcoplasmic reticulum (SR), containing ryanodine receptors (RyRs), and the sarcolemma, containing voltage- and Ca^2+-activated K^+ (BK) channels. These junctional microdomains promote hyperpolarization, reduced Cain, and relaxation. The second type is postulated to form around stretch-activated nonspecific cation channels and neighboring Ca^2+-activated Cl^− channels, and promotes the opposite (depolarization, increased Ca_in, and contraction). The model includes three additional compartments: the sarcoplasm, the central SR lumen, and the peripheral SR lumen. It incorporates 37 protein components. In addition to pressure, the model accommodates inputs of α- and β-adrenergic agonists, ATP, 11,12-epoxyeicosatrienoic acid, and nitric oxide (NO). The parameters of the equations were adjusted to obtain a close fit to reported Vm and Ca_in as functions of pressure, which have been determined in cerebral arteries. The simulations were insensitive to ±10% changes in most of the parameters. The model also simulated the effects of inhibiting RyR, BK, or voltage-activated Ca^2+ channels on V_m and Ca_in. Deletion of BK β1 subunits is known to increase arterial–SM tension. In the model, deletion of β1 raised Ca_in at all pressures, and these increases were reversed by NO

Motive-Oriented Psychotherapeutic Relationship Facing a Patient Presenting with Narcissistic Personality Disorder: A Case Study

Motive-oriented therapeutic relationship (MOTHER), a prescriptive concept based on an integrative form of case formulation, the Plan Analysis (PA) method (Caspar, in: Eells (ed.), Handbook of psychotherapy case formulations, 2007), has shown to be of particular relevance for the treatment of patients presenting with personality disorders, in particular contributing to better therapeutic outcome and to a more constructive development of the therapeutic alliance over time (Kramer et al., J Nerv Ment Dis 199:244–250, 2011). Several therapy models refer to MOTHER as intervention principle with regard to borderline and Narcissistic Personality Disorder (NPD) (Sachse et al., Clarification-oriented psychotherapy of narcissistic personality disorder, 2011; Caspar and Berger, in: Dulz et al. (eds.), Handbuch der Borderline-Störungen, 2011). The present case study discusses the case of Mark, a 40-year-old patient presenting with NPD, along with anxious, depressive and anger problems. This patient underwent a seven-session long pre-therapy process, based on psychiatric and psychotherapeutic principles complemented with PA and MOTHER, in preparation for further treatment. MOTHER will be illustrated with patient–therapist verbatim from session 4 and the links between MOTHER and confrontation techniques will be discussed in the context of process-outcome hypotheses, in particular the effect of MOTHER on symptom reduction. This research was supported by SNSF and funded by Grant No: 100014_134562/1

Siglec-1 on dendritic cells mediates SARS-CoV-2 trans-infection of target cells while on macrophages triggers proinflammatory responses

COVID-19 pandemic is not yet under control by vaccination, and effective antivirals are critical for preparedness. Here we report that macrophages and dendritic cells, key antigen presenting myeloid cells (APCs), are largely resistant to SARS-CoV-2 infection. APCs effectively captured viruses within cellular compartments that lead to antigen degradation. Macrophages sense SARS-CoV-2 and released higher levels of cytokines, including those related to cytokine storm in severe COVID-19. The sialic acid-binding Ig-like lectin 1 (Siglec-1/CD169) present on APCs, which interacts with sialylated gangliosides on membranes of retroviruses or filoviruses, also binds SARS-CoV-2 via GM1. Blockage of Siglec-1 receptors by monoclonal antibodies reduces SARS-CoV-2 uptake and transfer to susceptible target cells. APCs expressing Siglec-1 and carrying SARS-CoV-2 are found in pulmonary tissues of non-human primates. Single cell analysis reveals the in vivo induction of cytokines in those macrophages. Targeting Siglec-1 could offer cross-protection against SARS-CoV-2 and other enveloped viruses that exploit APCs for viral dissemination, including those yet to come in future outbreaks.The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. The authors also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). J.M-P. is supported by grant PID2019-109870RB-I00 from the Spanish Ministry of Science and Innovation and in part also by Grifols. CR lab is funded by RTI2018-094445-B100 (MCIU/AEI/FEDER, UE). The authors also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). The NHP study was primarily supported by YNPRC Coronavirus Pilot Research Project Program grant to M.Pa. under award P51 OD11132, Emergent Venture Fast grant program to MPa under awards #2206 and #2144, and William and Lula Pitts Foundation (to MPa).N

Author Correction to: SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells

Correction to: https://doi.org/10.1038/s41423-021-00794-6; http://hdl.handle.net/10261/257710In the version of this correspondence initially published, one of the SARS-CoV-2 variants used in Fig. 1B, which was originally described in the article as the SARS-CoV-2 variant ‘B.1.1.248.2 Gamma’, is actually the ‘P.2 Zeta’ SARS-CoV-2 variant of interest. The GISAID accession ID EPI_ISL_1831696 provided is correct, but it belongs to the Zeta variant. The results and conclusions are not affected by this unintentional inaccuracy.Peer reviewe