Protein Kinase C θ Affects Ca2+ Mobilization and NFAT Activation in Primary Mouse T Cells

Protein kinase C (PKC)θ is an established component of the immunological synapse and has been implicated in the control of AP-1 and NF-κB. To study the physiological function of PKCθ, we used gene targeting to generate a PKCθ null allele in mice. Consistently, interleukin 2 production and T cell proliferative responses were strongly reduced in PKCθ-deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKCθ primarily abrogates NFAT transactivation. In contrast, NF-κB activation was only partially reduced. This NFAT transactivation defect appears to be secondary to reduced inositol 1,4,5-trisphosphate generation and intracellular Ca2+ mobilization. Our finding suggests that PKCθ plays a critical and nonredundant role in T cell receptor–induced NFAT activation

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Aging-related tau astrogliopathy (ARTAG):harmonized evaluation strategy

Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators

Use of conspecific attraction to influence the breeding habitat selection of the Whinchat (Saxicola rubetra).

Kurzfassung Die Intensivierung der Grünlandbewirtschaftung und die zeitliche Verlagerung der Mahd sind zwei Hauptgründe für den drastischen Rückgang des Braunkehlchens (Saxicola rubetra) in West- und Mitteleuropa. Daher braucht es effektive Maßnahmen zur Förderung dieses Langstreckenziehers, der in der Schweiz subalpine Wiesen besiedelt. Die Tendenz von Individuen, sich in der Nähe von Artengenossen niederzulassen, wird als soziale Attraktion bezeichnet. Da Vögel die Anwesenheit von Artgenossen nutzen, um die Qualität des Habitats zu beurteilen, kann dieses Verhalten genutzt werden, um die Wahl des Bruthabitats eines Individuums zu beeinflussen. Bei verschiedenen Zugvögeln ist soziale Attraktion bereits erfolgreich als Instrument zur Artenförderung eingesetzt worden. Ziel dieser Studie war es experimentell zu testen, ob das Abspielen von arteigenen Gesängen die Wahl des Bruthabitats beim Braunkehlchen beeinflusst. Sollte diese Methode erfolgreich sein, kann das Abspielen von arteigenen Gesängen als Maßnahme zur Artenförderung genutzt werden, um die Ansiedlung des Braunkehlchens in geeignete, spät gemähte Gebiete zu lenken. Im selbigen Experiment wurde ebenfalls getestet, ob das Ausbringen von künstlichen Sing- und Sitzwarten zur Verbesserung der Habitatqualtät beiträgt und somit die Wahl des Bruthabitats für das Braunkehlchen beeinflusst. Dafür wurde 2018 im Unterengadin auf 79 Flächen ein kontrolliertes Playback-Experiment mit lokalen Braunkehlchengesängen durchgeführt. Darüber hinaus wurde der Einfluss von künstlichen Sing- und Sitzwarten getestet. Die Flächen wurden in drei verschiedene Qualitätsstufen (niedrig, mittel und hoch) eingeteilt und befanden sich entlang eines Distanzgradienten zu den bestehenden Kerngebieten. Sowohl das Playback-Experiment als auch die künstliche Erhöhung des Wartenangebots hatte keinen Einfluss auf die Wahl des Bruthabitats beim Braunkehlchen. Jedoch beeinflusste die Habitatqualität die Ansiedlung des Braunkehlchens, wobei Flächen tiefer Qualität gemieden wurden. Darüber hinaus zeigte das Ansiedlungsverhalten des Braunkehlchens ein starkes räumliches Muster, das von der Nähe zum nächsten Kerngebiet bestimmt wurde. Folglich besiedelten Braunkehlchen bevorzugt Flächen mittlerer und hoher Habitatqualität innerhalb von 2 km Distanz zum nächsten Kerngebiet. Das Abspielen von arteigenen Gesängen und Ausbringen von künstlichen Sing- und Sitzwarten sind als Maßnahme zur Artenförderung für das Braunkehlchen ungeeignet. Folglich sollten sich Förderungsmaßnamen auf den Schutz und die Aufwertung von bestehenden Kerngebieten und deren unmittelbare Umgebung im Umkreis von etwa 2 km fokussieren. Weitere Studien zur Bedeutung von sozialer Attraktion und dessen Einfluss auf die Wahl des Bruthabitats beim Braunkehlchen sind nötig, um den Zusammenhang von sozialen Faktoren, Standortstreue und Habitateigenschaften zu verdeutlichen.Abstract Background: Agricultural intensification of grasslands and shifts in the mowing phenology are the main reasons for the massive decline of the Whinchat (Saxicola rubetra) in Western and Central Europe. Hence, effective conservation measures are needed for this migratory songbird, which is in Switzerland confined to subalpine grasslands. Conspecific attraction, the tendency for individuals to settle near members of the same species, provides a conservation tool that has been successfully applied for several migratory passerines. Since birds use the presence of conspecifics as a cue to assess habitat quality, this behaviour can be exploited to influence the breeding habitat selection of individuals of a given species. Aims: This study aimed to test whether experimentally provided conspecific vocalizations influence the breeding habitat selection of the Whinchat. If successful, the playback of conspecific vocalizations could be used as a conservation measure to redirect settling Whinchats towards suitable areas that are unaffected by early mowing. Additionally, this experiment aimed at testing whether an increased availability of perches improves Whinchat habitat quality and therefore influences breeding habitat selection. Methods: In 2018, a controlled playback study using local conspecific vocalizations was conducted in the Lower Engadine on 79 experimental plots, which were simultaneously employed for testing the influence of an increased availability of perches. Established plots represented meadows of three different habitat quality levels (low, intermediate and high) along a distance gradient to existing large Whinchat populations (core areas). Results: The playback and the increased availability of perches did not affect the breeding habitat selection of the Whinchat. Nevertheless, the habitat quality influenced the species’ settlement, whereby low habitat quality plots were avoided. Furthermore, Whinchat settlement events were strongly related to the distance to the nearest core area. Consequently, Whinchats preferably settled in plots of high or intermediate habitat quality within approximately 2 km to the nearest core area. Conclusion: The playback of conspecific vocalizations and the use of artificial perches did not prove being useful tools for conservation measures. Conservation management for the Whinchat in the Lower Engadine must focus on the conservation and improvement of the existing large core areas and their surroundings up to 2 km distance. Further studies are necessary to address the importance of conspecific attraction for breeding habitat selection of the Whinchat and to unmask the relationship between social factors, breeding site fidelity and habitat characteristics

Diagnostic Accuracy of Electrical Impedance Spectroscopy in Non-melanoma Skin Cancer

Electrical impedance spectroscopy is a non-invasive technique that can help clinicians in diagnosing malignant skin tumours. Depending on the cellular irregularity of the lesion, electrical impedance spectroscopy can reveal changes in the structure and form of the cells, using a harmless electrical current applied to the skin. A score between 0 and 10 is generated by the electrical impedance spectrometer, where 0 is considered benign and 10 is malignant. This prospective study was conducted in 101 patients with a total of 200 skin lesions; 62 benign and 138 malignant. There was a significant difference between the electrical impedance of malignant and benign lesions (p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of electrical impedance spectroscopy for non-melanoma skin cancer were 94.2%, 41.9%, 78.3% and 76.5%, respectively, when the cut-off for the electrical impedance spectroscopy score was set between 5 and 6. The area under the curve in receiver operating characteristics analyses was 0.758