New sources, opportunities and challenges

Images of the Earth at night are an exceptional source of human geographical data, because artificial light highlights human activity in a way that daytime scenes do not. The quality of such imagery dramatically improved in 2012 with two new spaceborne detectors. The higher resolution and precision of the data considerably expands the scope of possible applications. In this paper, we introduce the two new data sources and discuss their potential limitations using three case studies. Data from the Visible Infrared Imaging Radiometer Suite Day-Night Band (VIIRS DNB) is shown to have sufficient resolution to identify major sources of waste light, such as airports, and we find considerable variation in the peak radiance of the world’s largest airports. Nighttime imagery brings “cultural footprints” to light: DNB data reveals that American cities emit many times more light per capita than German cities and that cities in the former East of Germany emit more light per capita than those in the former West. Photographs from the International Space Station, the second new source of imagery, provide some limited spectral information, as well as street-level resolution. These images may be of greater use for epidemiological studies than the lower resolution DNB data

Changes in creatine transporter function during cardiac maturation in the rat

<p>Abstract</p> <p>Background</p> <p>It is well established that the immature myocardium preferentially utilises non-oxidative energy-generating pathways. It exhibits low energy-transfer capacity via the creatine kinase (CK) shuttle, reflected in phosphocreatine (PCr), total creatine and CK levels that are much lower than those of adult myocardium. The mechanisms leading to gradually increasing energy transfer capacity during maturation are poorly understood. Creatine is not synthesised in the heart, but taken up exclusively by the action of the creatine transporter protein (CrT). To determine whether this transporter is ontogenically regulated, the present study serially examined CrT gene expression pattern, together with creatine uptake kinetics and resulting myocardial creatine levels, in rats over the first 80 days of age.</p> <p>Results</p> <p>Rats were studied during the late prenatal period (-2 days before birth) and 7, 13, 21, 33, 50 and 80 days after birth. Activity of cardiac citrate synthase, creatine kinase and its isoenzymes as well as lactate dehydrogenase (LDH) and its isoenzymes demonstrated the well-described shift from anaerobic towards aerobic metabolism. mRNA levels of CrT in the foetal rat hearts, as determined by real-time PCR, were about 30% of the mRNA levels in the adult rat heart and gradually increased during development. Creatine uptake in isolated perfused rat hearts increased significantly from 3.0 nmol/min/gww at 13 days old to 4.9 nmol/min/gww in 80 day old rats. Accordingly, total creatine content in hearts, measured by HPLC, increased steadily during maturation (30 nmol/mg protein (-2 days) vs 87 nmol/mg protein (80 days)), and correlated closely with CrT gene expression.</p> <p>Conclusions</p> <p>The maturation-dependant alterations of CK and LDH isoenzyme activities and of mitochondrial oxidative capacity were paralleled by a progressive increase of CrT expression, creatine uptake kinetics and creatine content in the heart.</p

Characterization of Antibiotic and Biocide Resistance Genes and Virulence Factors of Staphylococcus Species Associated with Bovine Mastitis in Rwanda

The present study was conducted from July to August 2018 on milk samples taken at dairy farms in the Northern Province and Kigali District of Rwanda in order to identify Staphylococcus spp. associated with bovine intramammary infection. A total of 161 staphylococcal isolates originating from quarter milk samples of 112 crossbred dairy cattle were included in the study. Antimicrobial susceptibility testing was performed and isolates were examined for the presence of various resistance genes. Staphylococcus aureus isolates were also analyzed for the presence of virulence factors, genotyped by spa typing and further phenotypically subtyped for capsule expression using Fourier Transform Infrared (FTIR) spectroscopy. Selected S. aureus were characterized using DNA microarray technology, multi-locus sequence typing (MLST) and whole-genome sequencing. All mecA-positive staphylococci were further genotyped using dru typing. In total, 14 different staphylococcal species were detected, with S. aureus being most prevalent (26.7%), followed by S. xylosus (22.4%) and S. haemolyticus (14.9%). A high number of isolates was resistant to penicillin and tetracycline. Various antimicrobial and biocide resistance genes were detected. Among S. aureus, the Panton–Valentine leukocidin (PVL) genes, as well as bovine leukocidin (LukM/LukF-P83) genes, were detected in two and three isolates, respectively, of which two also carried the toxic shock syndrome toxin gene tsst-1 bovine variant. t1236 was the predominant spa type. FTIR-based capsule serotyping revealed a high prevalence of non-encapsulated S. aureus isolates (89.5%). The majority of the selected S. aureus isolates belonged to clonal complex (CC) 97 which was determined using DNA microarray based assignment. Three new MLST sequence types were detected

Neurosensory Differentiation and Innervation Patterning in the Human Fetal Vestibular End Organs between the Gestational Weeks 8–12

Balance orientation depends on the precise operation of the vestibular end organs and the vestibular ganglion neurons. Previous research on the assemblage of the neuronal network in the developing fetal vestibular organ has been limited to data from animal models. Insights into the molecular expression profiles and signaling moieties involved in embryological development of the human fetal inner ear have been limited. We present an investigation of the cells of the vestibular end organs with specific focus on the hair cell differentiation and innervation pattern using an uninterrupted series of unique specimens from gestational weeks 8-12. Nerve fibers positive for peripherin innervate the entire fetal crista and utricle. While in rodents only the peripheral regions of the cristae and the extra-striolar region of the statolithic organs are stained. At week 9, transcription factors PAX2 and PAX8 were observed in the hair cells whereas PAX6 was observed for the first time among the supporting cells of the cristae and the satellite glial cells of the vestibular ganglia. Glutamine synthetase, a regulator of the neurotransmitter glutamate, is strongly expressed among satellite glia cells, transitional zones of the utricle and supporting cells in the sensory epithelium. At gestational week 11, electron microscopic examination reveals bouton contacts at hair cells and first signs of the formation of a protocalyx at type I hair cells. Our study provides first-hand insight into the fetal development of the vestibular end organs as well as their pattern of innervation by means of immunohistochemical and EM techniques, with the aim of contributing toward our understanding of balance development

Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy

BACKGROUND: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. RESULTS: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. CONCLUSIONS: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities

Citizen Science Provides Valuable Data for Monitoring Global Night Sky Luminance

The skyglow produced by artificial lights at night is one of the most dramatic anthropogenic modifications of Earth’s biosphere. The GLOBE at Night citizen science project allows individual observers to quantify skyglow using star maps showing different levels of light pollution. We show that aggregated GLOBE at Night data depend strongly on artificial skyglow, and could be used to track lighting changes worldwide. Naked eye time series can be expected to be very stable, due to the slow pace of human eye evolution. The standard deviation of an individual GLOBE at Night observation is found to be 1.2 stellar magnitudes. Zenith skyglow estimates from the ‘‘First World Atlas of Artificial Night Sky Brightness’’ are tested using a subset of the GLOBE at Night data. Although we find the World Atlas overestimates sky brightness in the very center of large cities, its predictions for Milky Way visibility are accurate

How Do Persons with Young and Late Onset Dementia Die?

Background: End of life symptoms and symptom management as well as the quality of dying (QoD) of persons with advanced dementia (PWAD) have not yet been systematically studied in Germany. Objective: 1) To investigate symptoms, treatment and care at the end of life, advance care planning, and circumstances of death of recently deceased PWAD;2) To determine whether there are differences between young and late onset dementia (YOD and LOD). Methods: The study was performed in the context of the project EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of Young-onset and Late-Onset dementia in Germany). Closest relatives of recently deceased patients with advanced YOD (N = 46) and LOD (N = 54) living at home or in long term care were interviewed. Results: Circumstances of death, symptoms, and treatment appeared to be similar between YOD and LOD, except that persons with LOD had significantly more somatic comorbidities and were admitted to hospital in the last three months of life more often than persons with LOD. At end of life, 60% of PWAD appeared to be at peace. Difficulty swallowing, gurgling, shortness of breath, and discomfort were observed most frequently. Large interindividual differences in suffering and QoD were present. Determinants of QoD were not identified. Conclusion: Our findings suggest that low QoD was caused by inadequate recognition and/or insufficient treatment of burdensome physical and emotional symptoms. PWADs' needs should be assessed regularly, and strategies focusing on treatment and implementing support for both the patient and caregiver must be established

Mutational profiles of metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab before and after secondary resection (AIO KRK 0306; FIRE-3)

Secondary resection of metastases is recommended in metastatic colorectal cancer (mCRC). Data describing changes in mutational profiles of corresponding primary tumor and metastatic tissue after conversion treatment are limited. Next generation sequencing was performed in formalin-fixed mCRC samples from patients of the FIRE-3 trial (FOLFIRI plus cetuximab or bevacizumab) before treatment start (baseline) and after secondary resection of metastases (post baseline). Changes of mutational profiles and tumor mutational burden (TMB) were assessed within a post-hoc analysis. Median overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between treatment arms. Paired tumor samples were obtained from 25 patients (19 RAS wild-type, 6 RAS mutant by pyrosequencing). ORR (92.0% vs 58.0%) and OS (60.8 vs 35.4 months, hazard ratio = 0.39 [95% CI 0.14-1.12], P = .08) were higher for patients receiving cetuximab. After conversion therapy, 56 alterations (42 in the cetuximab and 14 in the bevacizumab arm) were newly observed in 18 patients (9 each treated with cetuximab or bevacizumab). Gains (n = 21) and losses (n = 21) of alterations occurred during cetuximab-based treatment, while mainly gains of alterations occurred during bevacizumab (n = 10). Three of nine patients treated with cetuximab that presented a change of mutational profiles, developed resistance to cetuximab. Mutational profiles were largely comparable before and after treatment with anti-VEGF or anti-EGFR directed monoclonal antibodies after secondary resection. Mutations associated with resistance to anti-EGFR antibodies were observed in only one-third of patients

Generation of Leukaemia-Derived Dendritic Cells (DCleu) to improve anti-leukaemic activity in AML: selection of the most efficient response modifier combinations

Dendritic cells (DC) and leukaemia derived DC (DC(leu)) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from mononuclear cells in vitro following standard DC/DC(leu)-generating protocols. With respect to future clinical applications though, DC/DC(leu)-generating protocols specifically designed for application in a whole-blood-(WB)-environment must be established. Therefore, we developed ten new DC/DC(leu)-generating protocols (kits; Kit-A/-C/-D/-E/-F/-G/-H/-I/-K/-M) for the generation of DC/DC(leu) from leukaemic WB, containing calcium-ionophore, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), tumour-necrosis-factor-alpha, prostaglandin-E(1) (PGE(1)), prostaglandin-E(2) (PGE(2)) and/or picibanil (OK-432). All protocols were evaluated regarding their performance in generating DC/DC(leu) using refined classification and/or ranking systems; DC/DC(leu) were evaluated regarding their performance in stimulating anti-leukaemic activity using a cytotoxicity fluorolysis assay. Overall, we found the new kits capable to generate (mature) DC/DC(leu) from leukaemic WB. Through refined classification and ranking systems, we were able to select Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE(2)) and -M (GM-CSF + PGE(1)) as the most efficient kits in generating (mature) DC/DC(leu), which are further competent to stimulate immunoreactive cells to show an improved anti-leukaemic cytotoxicity as well. This great performance of Kit-I, -K and -M in mediating DC/DC(leu)-based anti-leukaemic immunity in a WB-environment in vitro constitutes an important and directive step for translating DC/DC(leu)-based immunotherapy of AML into clinical application