Embryological staging of the Zebra Finch, Taeniopygia guttata

Zebra Finches (Taeniopygia guttata) are the most commonly used laboratory songbird species, yet their embryological development has been poorly characterized. Most studies to date apply Hamburger and Hamilton stages derived from chicken development; however, significant differences in development between precocial and altricial species suggest that they may not be directly comparable. We provide the first detailed description of embryological development in the Zebra Finch under standard artificial incubation. These descriptions confirm that some of the features used to classify chicken embryos into stages are not applicable in an altricial bird such as the Zebra Finch. This staging protocol will help to standardize future studies of embryological development in the Zebra Finch. J. Morphol. 274:1090-1110, 2013. (c) 2013 Wiley Periodicals, Inc

The GAPS Experiment to Search for Dark Matter using Low-energy Antimatter

The GAPS experiment is designed to carry out a sensitive dark matter search by measuring low-energy cosmic ray antideuterons and antiprotons. GAPS will provide a new avenue to access a wide range of dark matter models and masses that is complementary to direct detection techniques, collider experiments and other indirect detection techniques. Well-motivated theories beyond the Standard Model contain viable dark matter candidates which could lead to a detectable signal of antideuterons resulting from the annihilation or decay of dark matter particles. The dark matter contribution to the antideuteron flux is believed to be especially large at low energies (E < 1 GeV), where the predicted flux from conventional astrophysical sources (i.e. from secondary interactions of cosmic rays) is very low. The GAPS low-energy antiproton search will provide stringent constraints on less than 10 GeV dark matter, will provide the best limits on primordial black hole evaporation on Galactic length scales, and will explore new discovery space in cosmic ray physics. Unlike other antimatter search experiments such as BESS and AMS that use magnetic spectrometers, GAPS detects antideuterons and antiprotons using an exotic atom technique. This technique, and its unique event topology, will give GAPS a nearly background-free detection capability that is critical in a rare-event search. GAPS is designed to carry out its science program using long-duration balloon flights in Antarctica. A prototype instrument was successfully flown from Taiki, Japan in 2012. GAPS has now been approved by NASA to proceed towards the full science instrument, with the possibility of a first long-duration balloon flight in late 2020. Here we motivate low-energy cosmic ray antimatter searches and discuss the current status of the GAPS experiment and the design of the payload.Comment: 8 pags, 3 figures, Proc. 35th International Cosmic Ray Conference (ICRC 2017), Busan, Kore

Genetic disruption of serine biosynthesis is a key driver of macular telangiectasia type 2 aetiology and progression.

BACKGROUND: Macular telangiectasia type 2 (MacTel) is a rare, heritable and largely untreatable retinal disorder, often comorbid with diabetes. Genetic risk loci subtend retinal vascular calibre and glycine/serine/threonine metabolism genes. Serine deficiency may contribute to MacTel via neurotoxic deoxysphingolipid production; however, an independent vascular contribution is also suspected. Here, we use statistical genetics to dissect the causal mechanisms underpinning this complex disease. METHODS: We integrated genetic markers for MacTel, vascular and metabolic traits, and applied Mendelian randomisation and conditional and interaction genome-wide association analyses to discover the causal contributors to both disease and spatial retinal imaging sub-phenotypes. RESULTS: Genetically induced serine deficiency is the primary causal metabolic driver of disease occurrence and progression, with a lesser, but significant, causal contribution of type 2 diabetes genetic risk. Conversely, glycine, threonine and retinal vascular traits are unlikely to be causal for MacTel. Conditional regression analysis identified three novel disease loci independent of endogenous serine biosynthetic capacity. By aggregating spatial retinal phenotypes into endophenotypes, we demonstrate that SNPs constituting independent risk loci act via related endophenotypes. CONCLUSIONS: Follow-up studies after GWAS integrating publicly available data with deep phenotyping are still rare. Here, we describe such analysis, where we integrated retinal imaging data with MacTel and other traits genomics data to identify biochemical mechanisms likely causing this disorder. Our findings will aid in early diagnosis and accurate prognosis of MacTel and improve prospects for effective therapeutic intervention. Our integrative genetics approach also serves as a useful template for post-GWAS analyses in other disorders

From planning the port/city to planning the port-city : exploring the economic interface in European port cities

In last three decades, planning agencies of most ports have institutionally evolved into a (semi-) independent port authority. The rationale behind this process is that port authorities are able to react more quickly to changing logistical and spatial preferences of maritime firms, hence increasing the competitiveness of ports. Although these dedicated port authorities have proven to be largely successful, new economic, social, and environmental challenges are quickly catching up on these port governance models, and particularly leads to (spatial) policy ‘conflicts’ between port and city. This chapter starts by assessing this conflict and argue that the conflict is partly a result of dominant—often also academic—spatial representations of the port city as two separate entities. To escape this divisive conception of contemporary port cities, this chapter presents a relational visualisation method that is able to analyse the economic interface between port and city. Based on our results, we reflect back on our proposition and argue that the core challenge today for researchers and policy makers is acknowledging the bias of port/city, being arguably a self-fulfilling prophecy. Hence, we turn the idea of (planning the) port/city conflicts into planning the port-city’s strengths and weaknesses

How impaired are children and adolescents by mental health problems? Results of the BELLA study

Background: The consideration of impairment plays a crucial role in detecting significant mental health problems in children whose symptoms do not meet diagnostic criteria. The assessment of impairment may be particularly relevant when only short screening instruments are applied in epidemiological surveys. Furthermore, differences between childrens’ and parents’ perceptions of present impairment and impairing symptoms are of interest with respect to treatment-seeking behaviour. Objectives: The objectives were to assess parent- and self-reported impairment due to mental health problems in a representative sample of children and adolescents; to describe the characteristics of highly impaired children with normal symptom scores; and to investigate the associations between symptoms in different problem areas and impairment. Methods: The mental health module of the German Health Interview and Examination Survey for Children and Adolescents (the BELLA study) examined mental health in a representative sub-sample of 2,863 families with children aged 7–17. Self-reported and parent-reported symptoms of mental health problems and associated impairment were identified by the extended version of the strengths and difficulties questionnaire (SDQ) in children 11 years and older. Results: Considerable levels of distress and functional impairment were found with 14.1% of the boys and 9.9% of the girls being severely impaired according to the parental reports. However, self-reported data shows a reversed gender-difference as well as lower levels of severe impairment (6.1% in boys; 10.0% in girls). Six percent of the sampled children suffer from pronounced impairment due to mental health problems but were not detected by screening for overall symptoms. Childrens’ and parents’ reports differed in regard to the association between reported symptom scores and associated impairment with children reporting higher impairment due to emotional problems. Conclusions: The assessment of impairment caused by mental health problems provides important information beyond the knowledge of symptoms and helps to identify an otherwise undetected high risk group. In the assessment of impairment, gender-specific issues have to be taken into account. Regarding the systematic differences between childrens’ and parents’ reports in the assessment of impairment, the child’s perspective should be given special attention

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases