PolarMorphism enables discovery of shared genetic variants across multiple traits from GWAS summary statistics

Pleiotropic SNPs are associated with multiple traits. Such SNPs can help pinpoint biological processes with an effect on multiple traits or point to a shared etiology between traits. We present PolarMorphism, a new method for the identification of pleiotropic SNPs from GWAS summary statistics. PolarMorphism can be readily applied to more than two traits or whole trait domains. PolarMorphism makes use of the fact that trait-specific SNP effect sizes can be seen as Cartesian coordinates and can thus be converted to polar coordinates r (distance from the origin) and theta (angle with the Cartesian x-axis). r describes the overall effect of a SNP, while theta describes the extent to which a SNP is shared. r and theta are used to determine the significance of SNP sharedness, resulting in a p-value per SNP that can be used for further analysis. We apply PolarMorphism to a large collection of publicly available GWAS summary statistics enabling the construction of a pleiotropy network that shows the extent to which traits share SNPs. This network shows how PolarMorphism can be used to gain insight into relationships between traits and trait domains. Furthermore, pathway analysis of the newly discovered pleiotropic SNPs demonstrates that analysis of more than two traits simultaneously yields more biologically relevant results than the combined results of pairwise analysis of the same traits. Finally, we show that PolarMorphism is more efficient and more powerful than previously published methods.

Observation of the crossover between metallic and insulating regimes of the spin Hall effect

The physics of the anomalous and spin Hall effects is one of the most intriguing aspects of condensed matter physics. An important finding from a large collection of experimental and theoretical results is the universal scaling of the anomalous or spin Hall conductivity with the electric conductivity. This scaling has been successfully described by the intrinsic Berry curvature and extrinsic scattering mechanisms for metallic systems, revealing the topological nature of these effects. In contrast, the underlying physics in the opposite limit, the disordered insulating regime, is still unclear. In particular, it remains a major challenge, both experimentally and theoretically, to explore the spin Hall effect in the insulating regime. Here, we report the observation of the crossover between the metallic and insulating regimes of the spin Hall effect. The result demonstrates a direct correspondence between the spin and anomalous Hall effects, which will advance the fundamental understanding of spin transport.

Pierre des Noyers, a scholar and scientific intermediary at the court of Louise-Marie Gonzaga

Pierre des Noyers, secretary of Queen of Poland Louise-Marie Gonzaga, is known for his role as a messenger, envoy, court journalist and sometimes propagandist. His work as an unofficial diplomat for the Queen and ambassador for France is less famous though no less interesting. Even though he was already quite involved in these time-consuming tasks, Pierre des Noyers also acted as a scientific intermediary for the quite curious Queen Louise-Marie of Poland. He maintained contacts with many scholars from France and Italy. He could nurture this network thanks to his position as an informal diplomat at the court of the Queen and his dedication to science in general. Even by discarding his most official and political letters, his known correspondence amounts to several hundred letters written in a period of around 50 years to various friends and scholars. Roberval, Gassendi, Boulliau, Hevelius or Pascal are among these contacts and he plays for most of them the role of a scientific intermediary sharing with them observations, books and anecdotes. His letters are filled with astronomical observations, prodigies and prophecies. Des Noyers was also a practitioner of science. Having possessed a rather large collection of scientific instruments he always sought the improved ones and his daily life was marked by scientific studies. He wrote meteorological bulletins for Academia del Cimento in Florence, studied the measurement of time, observed the sun and showed interest in the inner workings of the human body. This article will delve further into more scientific aspects of Pierre des Noyers’s life, both at the court of Louise-Marie and outside. The first part presents a rough overview of the secretary’s contacts in the scientific environment of 17th Century France and how they were used to connect scholars from Poland with this environment. The second part of this work presents Pierre des Noyers’s practice of science as a tool to understand the world and for which utmost diligence in measurement and practice is required. The last part focuses on des Noyers’s application of this scientific method in two, now pseudo-scientific fields: astrology and divination.

Contribution of Kramik Pustak Malika of Chatur Pandit in the field of Indian Music and its Relevance

Indian Classical Music is the best gift of Indian culture to the world. Indian Classical Music is of two types – उत्तर हिन्दुस्तानी संगीत पद्धति एवं दक्षिण हिन्दुस्तानी संगीत पद्धति. The roots of Indian Music are found in Vedas. Sanskrit is the ancient language and we found it in the Vedas. Many treatises related to music systems are also found in Sanskrit Language. To learn music properly, every learner has to go through two paths – 1. Theoretical music (Ancient treatises) 2. Practical Music (which follows Guru Shishya tradition). Pandit Bhatkhande has given wonderful and helpful notation system to Indian Classical Music. With the help of it he has collected many Bandish from different people and made a large collection. This collection is known as Kramik Pustak Malika. (Parts 1 -6). All these six parts are having theory of 150 ragas divided Thata-wise, with introductory chapter on the general theory of music, besides a short description of every Raga, followed by Svar-vistar. They contain about 1000 traditional compositions including Pandit Bhatkhande’s own compositions which are about 300 in notation. To know the Raga deeply, one can refer the same book and can get many Bandish, Svar-vistar, information about Ragas, their descriptions given in Sanskrit treatises, Thata (थाट), Tala, etc. Therefore, Kramik Pustak Malika of Chatur Pandit is the treasure of Indian Music.

An expanded toolkit for Drosophila gene tagging using synthesized homology donor constructs for CRISPR mediated homologous recombination

Previously, we described a large collection of Drosophila strains that each carry an artificial exon containing a T2AGAL4 cassette inserted in an intron of a target gene based on CRISPR-mediated homologous recombination (Lee et al., 2018). These alleles permit numerous applications and have proven to be very useful. Initially, the homologous recombination-based donor constructs had long homology arms (>500 bps) to promote precise integration of large constructs (>5kb). Recently, we showed that in vivo linearization of the donor constructs enables insertion of large artificial exons in introns using short homology arms (100-200 bps) (Kanca et al., 2019a). Shorter homology arms make it feasible to commercially synthesize homology donors and minimize the cloning steps for donor construct generation. Unfortunately, about 50% of Drosophila genes lack suitable coding introns for integration of artificial exons. Here, we report the development of new set of constructs that allow the replacement of the coding region of genes that lack suitable introns with a KozakGAL4 cassette, generating a knock-out/knock-in allele that expresses GAL4 similarly as the targeted gene. We also developed custom vector backbones to further facilitate and improve transgenesis. Synthesis of homology donor constructs in custom plasmid backbones that contain the target gene sgRNA obviates the need to inject a separate sgRNA plasmid and significantly increases the transgenesis efficiency. These upgrades will enable the targeting of nearly every fly gene, regardless of exon-intron structure, with a 70-80% success rate.

An extended toolkit for production and use of RVdG-CVS-N2c rabies viral vectors uncovers hidden hippocampal connections

From the large collection of molecular tools used to investigate neuronal connectivity, envA-pseudotyped rabies viral vectors (RVdGenvA) uniquely enable cell-type specific, trans-synaptic retrograde labeling. However, widespread use of the powerful and flexible method is to date hindered by low-yield and cumbersome production pipelines. Here, we report the development of new cell lines, which significantly reduce production time while increasing viral titer and eliminating background contamination from native-coat particles. We further show that RVdGenvA-CVS-N2c vectors produced using this system retain their enhanced retrograde-trafficking when compared with SAD-B19 vectors, allowing us to uncover undescribed cortico-hippocampal connections and to monitor activity in a cortical microcircuit of behaving animals. Along with new suites of AAV and RVdG-CVS-N2c vectors, developed to enable retrograde labeling from a wide range of neuronal populations and tailored for diverse experimental requirements, we present here an optimal system for mapping, manipulating and imaging of neuronal circuits.

Lemonia batavorum sp. nov. from the Netherlands, an overlooked sibling of L. dumi (Lepidoptera: Brahmaeidae)

Barcoding of Dutch specimens of Lemonia dumi (Linnaeus, 1761) (Lepidoptera: Brahmaeidae) and a study of a large collection material of this species resulted in discovery of a new, hitherto undescribed species Lemonia batavorum sp. nov. Based on comparison with L. dumi, species level of L. batavorum sp. nov. is supported by the differences in its external appearance, diff erences in genitalia of both sexes and by 1.92% p-distance to L. dumi as the nearest neighbour. Photographs of specimens and genitalia of both sexes are given.

Spectral theory of approximate lattices in nilpotent Lie groups

We consider approximate lattices in nilpotent Lie groups. With every such approximate lattice one can associate a hull dynamical system and, to every invariant measure of this system, a corresponding unitary representation. Our results concern both the spectral theory of the representation and the topological dynamics of the system. On the spectral side we construct explicit eigenfunctions for a large collection of central characters using weighted periodization against a twisted fiber density function. We construct this density function by establishing a parametric version of the Bombieri–Taylor conjecture and apply our results to locate high-intensity Bragg peaks in the central diffraction of an approximate lattice. On the topological side we show that under some mild regularity conditions the hull of an approximate lattice admits a sequence of continuous horizontal factors, where the final horizontal factor is abelian and each intermediate factor corresponds to a central extension. We apply this to extend theorems of Meyer and Dani–Navada concerning number-theoretic properties of Meyer sets to the nilpotent setting.

Grave developments

The burial site at Borre is a common example of centralization that took place in Scandinavia during the transition between the early and late Iron Age in the sixth century. The major activities of the site are dated to the Late Iron Age, ca. 550-1050 AD. The site, which is specifically known for its uncommonly large collection of monumental mounds, has often been referred to as a burial place for kings, and the mounds have been interpreted as symbols of power meant to solidify the control of the ruling elite. This article examines changes that take place during the sites use and discusses four possible phases based on a reworked chronology. The article argues that the phases are results of different societal needs and place the mounds in a larger setting than simply elitist constructions. The reworked chronology is based on a thorough Bayesian analysis and suggests some alterations to the current understanding of the chronology at Borre.