Expression of Wnt Signaling Components during Xenopus Pronephros Development

The formation of the vertebrate kidney is tightly regulated and relies on multiple evolutionarily conserved inductive events. These are present in the complex metanephric kidney of higher vertebrates, but also in the more primitive pronephric kidney functional in the larval stages of amphibians and fish. Wnts have long been viewed as central in this process. Canonical β-Catenin-dependent Wnt signaling establishes kidney progenitors and non-canonical β-Catenin-independent Wnt signaling participate in the morphogenetic processes that form the highly sophisticated nephron structure. While some individual Wnt signaling components have been studied extensively in the kidney, the overall pathway has not yet been analyzed in depth.Here we report a detailed expression analysis of all Wnt ligands, receptors and several downstream Wnt effectors during pronephros development in Xenopus laevis using in situ hybridization. Out of 19 Wnt ligands, only three, Wnt4, Wnt9a and Wnt11, are specifically expressed in the pronephros. Others such as Wnt8a are present, but in a broader domain comprising adjacent tissues in addition to the kidney. The same paradigm is observed for the Wnt receptors and its downstream signaling components. Fzd1, Fzd4, Fzd6, Fzd7, Fzd8 as well as Celsr1 and Prickle1 show distinct expression domains in the pronephric kidney, whereas the non-traditional Wnt receptors, Ror2 and Ryk, as well as the majority of the effector molecules are rather ubiquitous. In addition to this spatial regulation, the timing of expression is also tightly regulated. In particular, non-canonical Wnt signaling seems to be restricted to later stages of pronephros development.Together these data suggest a complex cross talk between canonical and non-canonical Wnt signaling is required to establish a functional pronephric kidney

Younger Than Ever? Subjective Age Is Becoming Younger and Remains More Stable in Middle-Age and Older Adults Today

Little is known about historical shifts in subjective age (i.e., how old individuals feel). Moving beyond the very few time-lagged cross-sectional cohort comparisons, we examined historical shifts in within-person trajectories of subjective age from midlife to advanced old age. We used cohort-comparative longitudinal data from middle-age and older adults in the German Ageing Survey (N = 14,928; ~50% female) who lived in Germany and were between 40 and 85 years old when entering the study. They provided up to seven observations over 24 years. Results revealed that being born later in historical time is associated with feeling younger by 2% every birth-year decade and with less intraindividual change toward an older subjective age. Women reported feeling younger than men; this gender gap widened across cohorts. The association of higher education with younger subjective age became weaker across cohorts. Potential reasons for the subjective-rejuvenation effect across cohorts are discussed.Bundesministerin für Frauen, Familien und Jugend https://doi.org/10.13039/501100011090Peer Reviewe

High-resolution expression profiling of selected gene sets during plant immune activation

The plant immune system involves detection of pathogens via both cell-surface and intracellular receptors. Both receptor classes can induce transcriptional reprogramming that elevates disease resistance. To assess differential gene expression during plant immunity, we developed and deployed quantitative sequence capture (CAP-I). We designed and synthesized biotinylated single-strand RNA bait libraries targeted to a subset of defense genes, and generated sequence capture data from 99 RNA-seq libraries. We built a data processing pipeline to quantify the RNA-CAP-I-seq data, and visualize differential gene expression. Sequence capture in combination with quantitative RNA-seq enabled cost-effective assessment of the expression profile of a specified subset of genes. Quantitative sequence capture is not limited to RNA-seq or any specific organism and can potentially be incorporated into automated platforms for high-throughput sequencing

Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care

Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat patients in short time frames, especially in remote locations with limited infrastructure. To overcome these barriers, we developed a platform using genetically engineered Pichia pastoris strains designed to secrete multiple proteins on programmable cues in an integrated, benchtop, millilitre-scale microfluidic device. We use this platform for rapid and switchable production of two biologics from a single yeast strain as specified by the operator. Our results demonstrate selectable and near-single-dose production of these biologics in <24 h with limited infrastructure requirements. We envision that combining this system with analytical, purification and polishing technologies could lead to a small-scale, portable and fully integrated personal biomanufacturing platform that could advance disease treatment at point-of-care

A national appraisal of haemodialysis vascular access provision in Scotland

Purpose: Published registry data demonstrate longstanding variation in the utilisation of different vascular access (VA) modalities between Scottish renal units; this may reflect different clinical processes between centres. A comprehensive appraisal was undertaken to understand the processes underpinning VA creation and maintenance across Scotland. Methods: A mixed methods approach was utilised. Fifty-two semi-structured interviews were conducted with patients and clinicians in all ten, adult and paediatric, Scottish renal units. Interview transcripts were subjected to thematic analysis. Clinical activity data were prospectively collected for six weeks, and correlated with registry data. Results: VA accounts for a large clinical workload. There was significant inter-centre variation in the utilisation of different VA modalities, and patients described frustrating, dissatisfying experiences. VA creation and maintenance pathways functioned best when nephrologists, surgeons and radiologists were co-located on the same campus with close multi-disciplinary working, protected clinical time, and proactive VA maintenance. No unit routinely measured or discussed procedure outcomes or strategic aspects of their service. Conclusions: Varied clinical outcomes reflected varied clinical processes. Optimised clinical pathways, staff education and measurement of clinical outcomes may improve VA service quality and facilitate safer, more effective, patient-centred care

Toroidal automorphic forms, Waldspurger periods and double Dirichlet series

The space of toroidal automorphic forms was introduced by Zagier in the 1970s: a GL_2-automorphic form is toroidal if it has vanishing constant Fourier coefficients along all embedded non-split tori. The interest in this space stems (amongst others) from the fact that an Eisenstein series of weight s is toroidal for a given torus precisely if s is a non-trivial zero of the zeta function of the quadratic field corresponding to the torus. In this paper, we study the structure of the space of toroidal automorphic forms for an arbitrary number field F. We prove that it decomposes into a space spanned by all derivatives up to order n-1 of an Eisenstein series of weight s and class group character omega precisely if s is a zero of order n of the L-series corresponding to omega at s, and a space consisting of exactly those cusp forms the central value of whose L-series is zero. The proofs are based on an identity of Hecke for toroidal integrals of Eisenstein series and a result of Waldspurger about toroidal integrals of cusp forms combined with non-vanishing results for twists of L-series proven by the method of double Dirichlet series.Comment: 14 page

Positive and negative affect are associated with salivary cortisol in the everyday life of older adults: A quantitative synthesis of four aging studies

Research on time-fluctuating links between positive affect and cortisol is inconsistent and mostly based on young to middle-aged samples. The current project investigated how moment-to-moment changes in positive and negative affect are associated with moment-to-moment changes in cortisol levels in older adults’ daily lives and whether those associations are moderated by differences in health status (as indicated by the number of comorbidities). Affect and cortisol data collected in four separately conducted momentary assessment studies with parallel protocols were pooled to obtain a sample of N=476 individuals aged 56–88 years (Mage=71.9, SD=6.6; 52% female). Participants provided affect reports and collected salivary cortisol 5–7 times a day for a 7-day period and reported the presence of 13 different health conditions. Data were analyzed using multilevel models, with time since waking, daily behaviors associated with cortisol secretion, age, and sex controlled. Feeling more positive affect than usual was associated with lower momentary cortisol. In contrast, feeling more negative affect than usual was associated with higher momentary cortisol. Associations of momentary positive and negative affect with cortisol were weaker among participants in worse as compared to those in better health. Trait positive affectivity was associated with more curvature of waking cortisol profiles and trait negative affectivity was associated with smaller cortisol awakening responses. Findings suggest that HPA axis responses fluctuate with everyday changes in positive and negative affect in older adults, and that higher HPA reactivity may indicate preserved health in this age group

First in vivo head-to-head comparison of high-definition versus standard-definition stent imaging with 64-slice computed tomography

The aim of this study was to compare image quality characteristics from 64-slice high definition (HDCT) versus 64-slice standard definition CT (SDCT) for coronary stent imaging. In twenty-five stents of 14 patients, undergoing contrast-enhanced CCTA both on 64-slice SDCT (LightSpeedVCT, GE Healthcare) and HDCT (Discovery HD750, GE Healthcare), radiation dose, contrast, noise and stent characteristics were assessed. Two blinded observers graded stent image quality (score 1=no, 2=mild, 3=moderate, and 4=severe artefacts). All scans were reconstructed with increasing contributions of adaptive statistical iterative reconstruction (ASIR) blending (0, 20, 40, 60, 80 and 100%). Image quality was significantly superior in HDCT versus SDCT (score 1.7±0.5 vs. 2.7±0.7; p<0.05). Image noise was significantly higher in HDCT compared to SDCT irrespective of ASIR contributions (p<0.05). Addition of 40% ASIR or more reduced image noise significantly in both HDCT and SDCT. In HDCT in-stent luminal attenuation was significantly lower and mean measured in-stent luminal diameter was significantly larger (1.2±0.4mm vs. 0.8±0.4mm; p<0.05) compared to SDCT. Radiation dose from HDCT was comparable to SDCT (1.8±0.7mSv vs. 1.7±0.7mSv; p=ns). Use of HDCT for coronary stent imaging reduces partial volume artefacts from stents yielding improved image quality versus SDCT at a comparable radiation dos